WILLIAMS SYNDROME A
3-in-1
Medical
Reference
A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers TO INTERNET REFERENCES
WILLIAMS SYNDROME A BIBLIOGRAPHY AND DICTIONARY FOR PHYSICIANS, PATIENTS, AND GENOME RESEARCHERS
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 7404 Trade Street San Diego, CA 92121 USA Copyright ©2007 by ICON Group International, Inc. Copyright ©2007 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher’s note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Williams Syndrome: A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers/ James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-11310-4 1. Williams Syndrome-Popular works.I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail:
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on Williams syndrome. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Chaired Professor of Management Science at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 7404 Trade Street San Diego, CA 92121 USA Fax: 858-635-9414 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON WILLIAMS SYNDROME .............................................................................. 3 Overview........................................................................................................................................ 3 Genetics Home Reference ............................................................................................................... 3 What Is Williams Syndrome? ........................................................................................................ 3 How Common Is Williams Syndrome?.......................................................................................... 4 What Are the Genetic Changes Related to Williams Syndrome? .................................................. 4 Where Can I Find Additional Information about Williams Syndrome?........................................ 5 References....................................................................................................................................... 7 What Is Chromosome 7? ................................................................................................................ 8 What Chromosomal Conditions Are Related to Chromosome 7? .................................................. 8 Is There a Standard Way to Diagram Chromosome 7?.................................................................. 9 References..................................................................................................................................... 10 What Is the Official Name of the CLIP2 Gene? ........................................................................... 11 What Is the Normal Function of the CLIP2 Gene?...................................................................... 11 What Conditions Are Related to the CLIP2 Gene?...................................................................... 12 Where Is the CLIP2 Gene Located?.............................................................................................. 12 References..................................................................................................................................... 12 What Is the Official Name of the ELN Gene? .............................................................................. 13 What Is the Normal Function of the ELN Gene?......................................................................... 13 What Conditions Are Related to the ELN Gene? ........................................................................ 13 Where Is the ELN Gene Located? ................................................................................................ 14 References..................................................................................................................................... 14 What Is the Official Name of the GTF2I Gene? ........................................................................... 15 What Is the Normal Function of the GTF2I Gene? ..................................................................... 15 What Conditions Are Related to the GTF2I Gene? ..................................................................... 15 Where Is the GTF2I Gene Located? ............................................................................................. 16 References..................................................................................................................................... 16 What Is the Official Name of the GTF2IRD1 Gene? ................................................................... 17 What Is the Normal Function of the GTF2IRD1 Gene?.............................................................. 17 What Conditions Are Related to the GTF2IRD1 Gene?.............................................................. 17 Where Is the GTF2IRD1 Gene Located?...................................................................................... 18 References..................................................................................................................................... 18 What Is the Official Name of the LIMK1 Gene?.......................................................................... 19 What Is the Normal Function of the LIMK1 Gene? .................................................................... 19 What Conditions Are Related to the LIMK1 Gene? .................................................................... 19 Where Is the LIMK1 Gene Located? ............................................................................................ 20 References..................................................................................................................................... 20 What Is the Official Name of the NCF1 Gene?............................................................................ 21 What Is the Normal Function of the NCF1 Gene? ...................................................................... 21 What Conditions Are Related to the NCF1 Gene? ...................................................................... 22 Where Is the NCF1 Gene Located? .............................................................................................. 22 References..................................................................................................................................... 23 Federally Funded Research on Williams Syndrome..................................................................... 23 The National Library of Medicine: PubMed ................................................................................ 47 CHAPTER 2. ALTERNATIVE MEDICINE AND WILLIAMS SYNDROME.............................................. 91 Overview...................................................................................................................................... 91 National Center for Complementary and Alternative Medicine.................................................. 91 Additional Web Resources ........................................................................................................... 93 General References ....................................................................................................................... 93
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CHAPTER 3. BOOKS ON WILLIAMS SYNDROME .............................................................................. 94 Overview...................................................................................................................................... 94 Book Summaries: Online Booksellers........................................................................................... 94 The National Library of Medicine Book Index ............................................................................. 96 CHAPTER 4. MULTIMEDIA ON WILLIAMS SYNDROME ................................................................... 97 Overview...................................................................................................................................... 97 Bibliography: Multimedia on Williams Syndrome ...................................................................... 97 APPENDIX A. HELP ME UNDERSTAND GENETICS ......................................................................... 99 Overview...................................................................................................................................... 99 The Basics: Genes and How They Work....................................................................................... 99 Genetic Mutations and Health................................................................................................... 110 Inheriting Genetic Conditions ................................................................................................... 116 Genetic Consultation ................................................................................................................. 124 Genetic Testing .......................................................................................................................... 126 Gene Therapy ............................................................................................................................. 132 The Human Genome Project and Genomic Research................................................................. 135 APPENDIX B. PHYSICIAN RESOURCES ........................................................................................... 138 Overview.................................................................................................................................... 138 NIH Guidelines.......................................................................................................................... 138 NIH Databases........................................................................................................................... 139 Other Commercial Databases..................................................................................................... 142 The Genome Project and Williams Syndrome ........................................................................... 142 APPENDIX C. PATIENT RESOURCES .............................................................................................. 146 Overview.................................................................................................................................... 146 Patient Guideline Sources.......................................................................................................... 146 Finding Associations.................................................................................................................. 148 Resources for Patients and Families........................................................................................... 149 ONLINE GLOSSARIES................................................................................................................ 151 Online Dictionary Directories ................................................................................................... 152 WILLIAMS SYNDROME DICTIONARY................................................................................. 154 INDEX .............................................................................................................................................. 197
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FORWARD In March 2001, the National Institutes of Health issued the following warning: “The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading.”1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with Williams syndrome is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about Williams syndrome, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to Williams syndrome, from the essentials to the most advanced areas of research. Special attention has been paid to present the genetic basis and pattern of inheritance of Williams syndrome. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on Williams syndrome. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to Williams syndrome, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. We hope these resources will prove useful to the widest possible audience seeking information on Williams syndrome. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/.
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CHAPTER 1. STUDIES ON WILLIAMS SYNDROME Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Williams syndrome. For those interested in basic information about Williams syndrome, we begin with a condition summary published by the National Library of Medicine.
Genetics Home Reference Genetics Home Reference (GHR) is the National Library of Medicine’s Web site for consumer information about genetic conditions and the genes or chromosomes responsible for those conditions. Here you can find a condition summary on Williams syndrome that describes the major features of the condition, provides information about the condition’s genetic basis, and explains its pattern of inheritance. In addition, a summary of the gene or chromosome related to Williams syndrome is provided.2 The Genetics Home Reference has recently published the following summary for Williams syndrome:
What Is Williams Syndrome?3 Williams syndrome is a developmental disorder that affects many parts of the body. This condition is characterized by mild to moderate mental retardation or learning disabilities, unique personality characteristics, distinctive facial features, and heart and blood vessel (cardiovascular) problems. Most people with Williams syndrome have some degree of mental retardation. They typically do better on tasks that involve spoken language and memorization than on visualspatial tasks such as writing and drawing. Affected individuals have outgoing, engaging 2 3
This section has been adapted from the National Library of Medicine: http://ghr.nlm.nih.gov/.
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/condition=williamssyndrome.
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Williams Syndrome
personalities and tend to take an extreme interest in other people. Attention deficit disorder (ADD), problems with anxiety, and phobias are common among people with this disorder. Young children with Williams syndrome have distinctive facial features including a broad forehead, a short nose with a broad tip, full cheeks, a wide mouth with full lips, and small, widely spaced teeth. In older children and adults, the face appears longer and gaunt. A form of cardiovascular disease called supravalvar aortic stenosis (SVAS) occurs frequently in people with Williams syndrome. Supravalvar aortic stenosis is a narrowing of the large blood vessel that carries blood from the heart to the rest of the body (the aorta). If this condition is not treated, the aortic narrowing can lead to shortness of breath, chest pain, and heart failure. Other problems with the heart and blood vessels, including high blood pressure (hypertension), have also been reported in people with Williams syndrome. Additional signs and symptoms of Williams syndrome include abnormalities of connective tissue (tissue that supports the body's joints and organs) such as joint problems and soft, loose skin. Affected people may also have increased calcium levels in the blood (hypercalcemia) in infancy, developmental delays, problems with coordination, and short stature. Medical problems involving the eyes and vision, the digestive tract, and the urinary system are also possible.
How Common Is Williams Syndrome? An estimated 1 in 7,500 to 20,000 people is born with Williams syndrome.
What Are the Genetic Changes Related to Williams Syndrome? Williams syndrome is a chromosomal condition related to chromosome 7 (http://ghr.nlm.nih.gov/chromosome=7). The CLIP2 (http://ghr.nlm.nih.gov/gene=clip2), ELN (http://ghr.nlm.nih.gov/gene=eln), GTF2I (http://ghr.nlm.nih.gov/gene=gtf2i), GTF2IRD1 (http://ghr.nlm.nih.gov/gene=gtf2ird1), LIMK1 (http://ghr.nlm.nih.gov/gene=limk1), and NCF1 (http://ghr.nlm.nih.gov/gene=ncf1) genes are associated with Williams syndrome. Williams syndrome is caused by the deletion of genetic material from a specific region of chromosome 7. The deleted region includes more than 20 genes, and researchers believe that a loss of several of these genes probably contributes to the characteristic features of this disorder. CLIP2, ELN, GTF2I, GTF2IRD1, and LIMK1 are among the genes that are typically deleted in people with Williams syndrome. Researchers have found that loss of the ELN gene is associated with the connective tissue abnormalities and cardiovascular disease (specifically supravalvar aortic stenosis) found in many people with this disease. Studies suggest that deletion of LIMK1, GTF2I, GTF2IRD1, and perhaps other genes may help explain the characteristic difficulties with visual-spatial tasks. Loss of the GRF2IRD1 may also be partly responsible for the distinctive facial features often associated with Williams syndrome. Additionally, there is evidence that the deletion of several of these genes, including CLIP2,
Studies
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may contribute to the unique behavioral characteristics, mental retardation, and other cognitive difficulties seen in this condition. The NCF1 gene is also deleted in some people with Williams syndrome. Researchers have found that the loss of this gene appears to lower the risk of developing hypertension in some affected individuals. The relationship between other genes in the deleted region of chromosome 7 and the signs and symptoms of Williams syndrome is unknown.
Where Can I Find Additional Information about Williams Syndrome? You may find the following resources about Williams syndrome helpful. These materials are written for the general public. NIH Publications - National Institutes of Health •
National Center for Biotechnology Information: Genes and Disease: http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.189
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National Institute of Neurological Disorders and Stroke: http://www.ninds.nih.gov/disorders/williams/williams.htm
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NIH News Release: Scientists Uncover New Clues About Brain Function in Human Behavior (July 10, 2005): http://www.nih.gov/news/pr/jul2005/nimh-10.htm MedlinePlus - Health Information
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Encyclopedia: Williams syndrome: http://www.nlm.nih.gov/medlineplus/ency/article/001116.htm
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Health Topic: Developmental Disabilities: http://www.nlm.nih.gov/medlineplus/developmentaldisabilities.html
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Health Topic: Heart Diseases: http://www.nlm.nih.gov/medlineplus/heartdiseases.html
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Health Topic: Neurologic Diseases: http://www.nlm.nih.gov/medlineplus/neurologicdiseases.html Educational Resources - Information Pages
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California Department of Developmental Services: http://www.ddhealthinfo.org/ggrc/doc2.asp?ParentID=3176
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Center for Craniofacial Development and Disorders, Johns Hopkins Medicine: http://www.hopkinsmedicine.org/craniofacial/Education/DefinedArticle.cfm?ArticleI D=99&Source=Family&LayArticle=Yes
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Genetic Science Learning Center, University of Utah: http://gslc.genetics.utah.edu/units/disorders/karyotype/williams.cfm
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Madisons Foundation: http://www.madisonsfoundation.org/content/3/1/display.asp?did=227
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New York Online Access to Health (NOAH): http://www.noah-health.org/en/genetic/conditions/william.html
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Orphanet: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=904
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University of Nevada School of Medicine: http://www.unr.edu/med/dept/Genetics/Williams.html Patient Support - for Patients and Families
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Chromosome Deletion Outreach: http://www.chromodisorder.org/
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Family Village: http://www.familyvillage.wisc.edu/lib_will.htm
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National Organization for Rare Disorders: http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Williams+Synd rome
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Resource list from the University of Kansas Medical Center: http://www.kumc.edu/gec/support/williams.html
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Williams Syndrome Comprehensive Web Site: http://www.wsf.org Professional Resources
You may also be interested in these resources, which are designed for healthcare professionals and researchers. •
Gene Reviews - Clinical summary: http://www.genetests.org/query?dz=williams
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Gene Tests - DNA tests ordered by healthcare professionals: http://www.genetests.org/query?testid=2527
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ClinicalTrials.gov - Linking patients to medical research: http://clinicaltrials.gov/search/condition=%22williams+syndrome%22?recruiting=fals
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PubMed - Recent literature: http://ghr.nlm.nih.gov/condition=williamssyndrome/show/PubMed;jsessionid=03441 A5067AE49DD569B8E7A9D34ACCCe
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Online Books - Medical and science texts: http://books.mcgrawhill.com/getommbid.php?isbn=0071459960&template=ommbid&c=65
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OMIM - Genetic disorder catalog: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=194050
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References These sources were used to develop the Genetics Home Reference condition summary on Williams syndrome. •
Bhattacharjee Y. Friendly faces and unusual minds. Science. 2005 Nov 4;310(5749):802-4. No abstract available. PubMed citation
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Carrasco X, Castillo S, Aravena T, Rothhammer P, Aboitiz F. Williams syndrome: pediatric, neurologic, and cognitive development. Pediatr Neurol. 2005 Mar;32(3):16672. PubMed citation
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Emery, Alan E H; Rimoin, David L; Emery & Rimoin's principles and practice of medical genetics.; 4th ed. / edited by David L. Rimoin. [et al.]; London; New York : Churchill Livingstone, 2002. p1220-1222. NLM Catalog
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Gene Review: Williams Syndrome
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Mervis CB. Williams syndrome: 15 years of psychological research. Dev Neuropsychol. 2003;23(1-2):1-12. Review. PubMed citation
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Meyer-Lindenberg A, Hariri AR, Munoz KE, Mervis CB, Mattay VS, Morris CA, Berman KF. Neural correlates of genetically abnormal social cognition in Williams syndrome. Nat Neurosci. 2005 Jul 10; [Epub ahead of print]. PubMed citation
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Meyer-Lindenberg A, Mervis CB, Berman KF. Neural mechanisms in Williams syndrome: a unique window to genetic influences on cognition and behaviour. Nat Rev Neurosci. 2006 May;7(5):380-93. Review. PubMed citation
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Morris CA, Mervis CB. Williams syndrome and related disorders. Annu Rev Genomics Hum Genet. 2000;1:461-84. Review. PubMed citation
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Pankau R, Siebert R, Kautza M, Schneppenheim R, Gosch A, Wessel A, Partsch CJ. Familial Williams-Beuren syndrome showing varying clinical expression. Am J Med Genet. 2001 Feb 1;98(4):324-9. Review. PubMed citation
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Scriver, Charles R; The metabolic & molecular bases of inherited disease; 8th ed.; New York : McGraw-Hill, c2001. p1302-1303. NLM Catalog
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Tassabehji M, Hammond P, Karmiloff-Smith A, Thompson P, Thorgeirsson SS, Durkin ME, Popescu NC, Hutton T, Metcalfe K, Rucka A, Stewart H, Read AP, Maconochie M, Donnai D. GTF2IRD1 in craniofacial development of humans and mice. Science. 2005 Nov 18;310(5751):1184-7. Epub 2005 Nov 3. PubMed citation
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Tassabehji M. Williams-Beuren syndrome: a challenge for genotype-phenotype correlations. Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R229-37. Epub 2003 Sep 2. Review. PubMed citation
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Williams Syndrome
A summary of the chromosome and genes related to Williams syndrome is provided below:
What Is Chromosome 7?4 Humans normally have 46 chromosomes in each cell, divided into 23 pairs. Two copies of chromosome 7, one copy inherited from each parent, form one of the pairs. Chromosome 7 spans about 159 million base pairs (the building blocks of DNA) and represents more than 5 percent of the total DNA in cells. Identifying genes on each chromosome is an active area of genetic research. Because researchers use different approaches to predict the number of genes on each chromosome, the estimated number of genes varies. Chromosome 7 likely contains between 1,000 and 1,500 genes. Genes on chromosome 7 are among the estimated 20,000 to 25,000 total genes in the human genome. There are many genetic conditions related to genes on chromosome 7.
What Chromosomal Conditions Are Related to Chromosome 7? The following conditions are caused by changes in the structure or number of copies of chromosome 7. Cancers Changes in the number or structure of chromosome 7 occur frequently in human cancers. These changes are typically somatic, which means they are acquired during a person's lifetime and are present only in tumor cells. Many forms of cancer are associated with damage to chromosome 7. In particular, changes in this chromosome have been identified in cancers of blood-forming tissue (leukemias) and cancers of immune system cells (lymphomas). A loss of part or all of one copy of chromosome 7 is common in myelodysplastic syndrome, which is a disease of the blood and bone marrow. People with this disorder have an increased risk of developing leukemia. Greig Cephalopolysyndactyly Syndrome Abnormalities of chromosome 7 are responsible for some cases of Greig cephalopolysyndactyly syndrome. These chromosomal changes involve a region of the short (p) arm of chromosome 7 that contains the GLI3 gene. This gene plays an important role in the development of many tissues and organs before birth. In some cases, Greig cephalopolysyndactyly syndrome results from a rearrangement (translocation) of genetic material between chromosome 7 and another chromosome. Other cases are caused by the deletion of several genes, including GLI3, from the short arm of chromosome 7. The loss of 4
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/chromosome=7;jsessionid=03441A5067AE49DD569B8E7A9D34ACCC.
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multiple genes can cause a more severe form of this disorder called Greig cephalopolysyndactyly contiguous gene deletion syndrome. People with this form of the disorder have characteristic developmental problems involving the limbs, head, and face along with seizures, mental retardation, and developmental delay. Williams Syndrome Williams syndrome is caused by the deletion of genetic material from a portion of the long (q) arm of chromosome 7. The deleted region, which is located at position 11.23 (written as 7q11.23), is designated the Williams syndrome critical region. This region includes more than 20 genes, and researchers believe that the characteristic features of Williams syndrome are probably related to the loss of several of these genes. Other Chromosomal Conditions Other changes in the number or structure of chromosome 7 can cause delayed growth and development, mental retardation, distinctive facial features, skeletal abnormalities, delayed speech, and other medical problems. Changes in chromosome 7 include an extra copy of some genetic material from this chromosome in each cell (partial trisomy 7) or a missing segment of the chromosome in each cell (partial monosomy 7). In some cases, several DNA building blocks (nucleotides) are abnormally deleted or duplicated in part of chromosome 7. A circular structure called ring chromosome 7 is also possible. Ring chromosomes occur when a chromosome breaks in two places and the ends of the chromosome arms fuse together to form a circular structure.
Is There a Standard Way to Diagram Chromosome 7? Geneticists use diagrams called ideograms as a standard representation for chromosomes. Ideograms show a chromosome's relative size and its banding pattern. A banding pattern is the characteristic pattern of dark and light bands that appears when a chromosome is stained with a chemical solution and then viewed under a microscope. These bands are used to describe the location of genes on each chromosome.
You may find the following resources about chromosome 7 helpful. These materials are written for the general public. You may also be interested in these resources, which are designed for genetics professionals and researchers.
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Williams Syndrome
References These sources were used to develop the Genetics Home Reference chromosome summary on chromosome 7. •
Ensembl Human Map View: Chromosome 7
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Gene Review: Greig Cephalopolysyndactyly Syndrome
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Gene Review: Williams Syndrome
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Gilbert F. Chromosome 7. Genet Test. 2002 Summer;6(2):141-61. No abstract available. PubMed citation
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Hasle H, Olsen JH, Hansen J, Friedrich U, Tommerup N. Occurrence of cancer in a cohort of 183 persons with constitutional chromosome 7 abnormalities. Cancer Genet Cytogenet. 1998 Aug;105(1):39-42. Review. PubMed citation
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Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK. The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. PubMed citation
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Johnston JJ, Olivos-Glander I, Turner J, Aleck K, Bird LM, Mehta L, Schimke RN, Heilstedt H, Spence JE, Blancato J, Biesecker LG. Clinical and molecular delineation of the Greig cephalopolysyndactyly contiguous gene deletion syndrome and its distinction from acrocallosal syndrome. Am J Med Genet A. 2003 Dec 15;123(3):236-42. PubMed citation
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Kroisel PM, Petek E, Wagner K. Phenotype of five patients with Greig syndrome and microdeletion of 7p13. Am J Med Genet. 2001 Aug 15;102(3):243-9. PubMed citation
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Le Beau MM, Espinosa R 3rd, Davis EM, Eisenbart JD, Larson RA, Green ED. Cytogenetic and molecular delineation of a region of chromosome 7 commonly deleted in malignant myeloid diseases. Blood. 1996 Sep 15;88(6):1930-5. PubMed citation
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Lichtenbelt KD, Hochstenbach R, van Dam WM, Eleveld MJ, Poot M, Beemer FA. Supernumerary ring chromosome 7 mosaicism: case report, investigation of the gene content, and delineation of the phenotype. Am J Med Genet A. 2005 Jan 1;132(1):93-100. Review. PubMed citation
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Map Viewer: Genes on Sequence
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Pai, G Shashidhar; Lewandowski, Raymond C; Borgaonkar, Digamber S; Handbook of chromosomal syndromes; Hoboken, N.J. : Wiley-Liss, c2003. p96-114. NLM Catalog
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Rodriguez L, Lopez F, Paisan L, de la Red Mdel M, Ruiz AM, Blanco M, Antelo Cortizas J, Martinez-Frias ML. Pure partial trisomy 7q: two new patients and review. Am J Med Genet. 2002 Nov 22;113(2):218-24. Review. PubMed citation
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Scherer SW, Cheung J, MacDonald JR, Osborne LR, Nakabayashi K, Herbrick JA, Carson AR, Parker-Katiraee L, Skaug J, Khaja R, Zhang J, Hudek AK, Li M, Haddad M, Duggan GE, Fernandez BA, Kanematsu E, Gentles S, Christopoulos CC, Choufani S, Kwasnicka D, Zheng XH, Lai Z, Nusskern D, Zhang Q, Gu Z, Lu F, Zeesman S, Nowaczyk MJ, Teshima I, Chitayat D, Shuman C, Weksberg R, Zackai EH, Grebe TA, Cox SR, Kirkpatrick SJ, Rahman N, Friedman JM, Heng HH, Pelicci PG, Lo-Coco F, Belloni E, Shaffer LG, Pober B, Morton CC, Gusella JF, Bruns GA, Korf BR, Quade BJ, Ligon AH, Ferguson H, Higgins AW, Leach NT, Herrick SR, Lemyre E, Farra CG, Kim HG, Summers AM, Gripp KW, Roberts W, Szatmari P, Winsor EJ, Grzeschik KH, Teebi A, Minassian BA, Kere J, Armengol L, Pujana MA, Estivill X, Wilson MD, Koop BF, Tosi S, Moore GE, Boright AP, Zlotorynski E, Kerem B, Kroisel PM, Petek E, Oscier DG, Mould SJ, Dohner H, Dohner K, Rommens JM, Vincent JB, Venter JC, Li PW, Mural RJ, Adams MD, Tsui LC. Human chromosome 7: DNA sequence and biology. Science. 2003 May 2;300(5620):767-72. Epub 2003 Apr 10. PubMed citation
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UCSC Genome Browser: Statistics from NCBI Build 36.1, March 2006
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Velagaleti GV, Jalal SM, Kukolich MK, Lockhart LH, Tonk VS. De novo supernumerary ring chromosome 7: first report of a non-mosaic patient and review of the literature. Clin Genet. 2002 Mar;61(3):202-6. Review. PubMed citation
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Zenklusen JC, Conti CJ. Cytogenetic, molecular and functional evidence for novel tumor suppressor genes on the long arm of human chromosome 7. Mol Carcinog. 1996 Mar;15(3):167-75. Review. No abstract available. PubMed citation
What Is the Official Name of the CLIP2 Gene?5 The official name of this gene is “CAP-GLY domain containing linker protein 2.” CLIP2 is the gene's official symbol. The CLIP2 gene is also known by other names, listed below.
What Is the Normal Function of the CLIP2 Gene? The CLIP2 gene provides instructions for making a protein called CAP-GLY domain containing linker protein 2 or CLIP-115. This protein is found predominantly in the brain, where it likely plays a role in the normal structure and function of nerve cells. Within cells, this protein is thought to regulate aspects of the cytoskeleton, the structural framework that helps to determine cell shape, size, and movement. The protein is associated with microtubules, which are rigid, hollow fibers that make up a significant part of the cytoskeleton. Microtubules help cells maintain their shape, assist in the process of cell division, and are essential for the transport of materials within cells.
5
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/gene=clip2.
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Williams Syndrome
What Conditions Are Related to the CLIP2 Gene? Williams Syndrome - Associated with the CLIP2 Gene The CLIP2 gene is located in a region of chromosome 7 that is deleted in people with Williams syndrome. As a result of this deletion, people with this condition are missing one copy of the CLIP2 gene in each cell. Studies suggest that the loss of this gene may contribute to some of the characteristic features of Williams syndrome, including unique behavioral traits and symptoms that affect the nervous system. A deletion of this gene probably disrupts the normal regulation of the cytoskeleton and affects the structure of nerve cells in the brain. It is not known how these changes may be related to the characteristic signs and symptoms of Williams syndrome.
Where Is the CLIP2 Gene Located? Cytogenetic Location: 7q11.23 Molecular Location on chromosome 7: base pairs 73,341,740 to 73,458,200
The CLIP2 gene is located on the long (q) arm of chromosome 7 at position 11.23. More precisely, the CLIP2 gene is located from base pair 73,341,740 to base pair 73,458,200 on chromosome 7.
References These sources were used to develop the Genetics Home Reference gene summary on the CLIP2 gene. •
De Zeeuw CI, Hoogenraad CC, Goedknegt E, Hertzberg E, Neubauer A, Grosveld F, Galjart N. CLIP-115, a novel brain-specific cytoplasmic linker protein, mediates the localization of dendritic lamellar bodies. Neuron. 1997 Dec;19(6):1187-99. PubMed citation
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Hoogenraad CC, Akhmanova A, Galjart N, De Zeeuw CI. LIMK1 and CLIP-115: linking cytoskeletal defects to Williams syndrome. Bioessays. 2004 Feb;26(2):141-50. Review. PubMed citation
Studies
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Hoogenraad CC, Akhmanova A, Grosveld F, De Zeeuw CI, Galjart N. Functional analysis of CLIP-115 and its binding to microtubules. J Cell Sci. 2000 Jun;113 ( Pt 12):2285-97. PubMed citation
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Meyer-Lindenberg A, Mervis CB, Sarpal D, Koch P, Steele S, Kohn P, Marenco S, Morris CA, Das S, Kippenhan S, Mattay VS, Weinberger DR, Berman KF. Functional, structural, and metabolic abnormalities of the hippocampal formation in Williams syndrome. J Clin Invest. 2005 Jul 1;115(7):1888-1895. Epub 2005 Jun 9. PubMed citation
What Is the Official Name of the ELN Gene?6 The official name of this gene is “elastin (supravalvular aortic stenosis, Williams-Beuren syndrome).” ELN is the gene's official symbol. The ELN gene is also known by other names, listed below.
What Is the Normal Function of the ELN Gene? The ELN gene provides instructions for making a protein called elastin, which is the major component of elastic fibers. Elastic fibers are slender bundles of proteins that provide strength and flexibility to connective tissues (tissues that support the body's joints and organs). Elastic fibers are found in the intricate lattice that forms in the spaces between cells (the extracellular matrix), where they give structural support to organs and tissues such as the heart, skin, lungs, ligaments, and blood vessels.
What Conditions Are Related to the ELN Gene? Williams Syndrome - Associated with the ELN Gene The ELN gene is located in a region of chromosome 7 that is deleted in people with Williams syndrome. As a result of this deletion, people with Williams syndrome are missing one copy of the ELN gene in each cell. This loss reduces the production of elastin by half, which disrupts the normal structure of elastic fibers in many connective tissues. Large blood vessels with abnormal elastic fibers are often thicker and less resilient than normal. These vessels can narrow, increasing the resistance to normal blood flow and leading to serious medical problems. Other Disorders - Caused by Mutations in the ELN Gene The ELN gene is located in a region of chromosome 7 that is deleted in people with Williams syndrome. As a result of this deletion, people with Williams syndrome are missing one copy of the ELN gene in each cell. This loss reduces the production of elastin by half, which disrupts the normal structure of elastic fibers in many connective tissues. Large blood vessels with abnormal elastic fibers are often thicker and less resilient than normal. These 6
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/gene=eln;jsessionid=03441A5067AE49DD569B8E7A9D34ACCC.
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Williams Syndrome
vessels can narrow, increasing the resistance to normal blood flow and leading to serious medical problems.
Where Is the ELN Gene Located? Cytogenetic Location: 7q11.23 Molecular Location on chromosome 7: base pairs 73,080,453 to 73,120,965
The ELN gene is located on the long (q) arm of chromosome 7 at position 11.23. More precisely, the ELN gene is located from base pair 73,080,453 to base pair 73,120,965 on chromosome 7.
References These sources were used to develop the Genetics Home Reference gene summary on the ELN gene. •
Gene Review: Williams Syndrome
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Metcalfe K, Rucka AK, Smoot L, Hofstadler G, Tuzler G, McKeown P, Siu V, Rauch A, Dean J, Dennis N, Ellis I, Reardon W, Cytrynbaum C, Osborne L, Yates JR, Read AP, Donnai D, Tassabehji M. Elastin: mutational spectrum in supravalvular aortic stenosis. Eur J Hum Genet. 2000 Dec;8(12):955-63. PubMed citation
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Milewicz DM, Urban Z, Boyd C. Genetic disorders of the elastic fiber system. Matrix Biol. 2000 Nov;19(6):471-80. Review. PubMed citation
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Morris CA, Mervis CB. Williams syndrome and related disorders. Annu Rev Genomics Hum Genet. 2000;1:461-84. Review. PubMed citation
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Rodriguez-Revenga L, Badenas C, Carrio A, Mila M. Elastin mutation screening in a group of patients affected by vascular abnormalities. Pediatr Cardiol. 2005 NovDec;26(6):827-31. PubMed citation
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Rodriguez-Revenga L, Iranzo P, Badenas C, Puig S, Carrio A, Mila M. A novel elastin gene mutation resulting in an autosomal dominant form of cutis laxa. Arch Dermatol. 2004 Sep;140(9):1135-9. Review. PubMed citation
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Szabo Z, Crepeau MW, Mitchell AL, Stephan MJ, Puntel RA, Yin Loke K, Kirk RC, Urban Z. Aortic aneurysmal disease and cutis laxa caused by defects in the elastin gene. J Med Genet. 2006 Mar;43(3):255-8. Epub 2005 Aug 5. PubMed citation
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Tassabehji M. Williams-Beuren syndrome: a challenge for genotype-phenotype correlations. Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R229-37. Epub 2003 Sep 2. Review. PubMed citation
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Urban Z, Riazi S, Seidl TL, Katahira J, Smoot LB, Chitayat D, Boyd CD, Hinek A. Connection between elastin haploinsufficiency and increased cell proliferation in patients with supravalvular aortic stenosis and Williams-Beuren syndrome. Am J Hum Genet. 2002 Jul;71(1):30-44. Epub 2002 May 6. PubMed citation
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Urban Z, Zhang J, Davis EC, Maeda GK, Kumar A, Stalker H, Belmont JW, Boyd CD, Wallace MR. Supravalvular aortic stenosis: genetic and molecular dissection of a complex mutation in the elastin gene. Hum Genet. 2001 Nov;109(5):512-20. Epub 2001 Oct 13. PubMed citation
What Is the Official Name of the GTF2I Gene?7 The official name of this gene is “general transcription factor II, i.” GTF2I is the gene's official symbol. The GTF2I gene is also known by other names, listed below.
What Is the Normal Function of the GTF2I Gene? The GTF2I gene provides instructions for making two proteins, BAP-135 and TFII-I. BAP135 is involved in normal immune system function. It is active in B cells, which are a specialized type of white blood cell that protects the body against infection. When a B cell senses a foreign substance (such as a virus), it triggers a series of chemical reactions that instruct the cell to mature, divide, and produce specific proteins called antibodies to fight the infection. The BAP-135 protein is activated as part of this series of chemical reactions; it transmits chemical signals that allow B cells to respond to potentially harmful invaders. TFII-I, the other protein produced by the GTF2I gene, binds to specific areas of DNA and helps regulate the activity of other genes. Based on this role, TFII-I is called a transcription factor. This protein is active in many types of tissue, particularly in the brain, but its exact function has not been determined.
What Conditions Are Related to the GTF2I Gene? Williams Syndrome - Associated with the GTF2I Gene The GTF2I gene is located in a region of chromosome 7 that is deleted in people with Williams syndrome. As a result of this deletion, people with this condition are missing one 7
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/gene=gtf2i.
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Williams Syndrome
copy of the GTF2I gene in each cell. Studies suggest that the loss of this gene is partly responsible for mental retardation in people with Williams syndrome. Loss of this gene may also contribute to the characteristic problems with visual-spatial tasks (such as writing and drawing) seen in this disorder. Researchers are investigating how a deletion involving this gene may be related to these specific features of Williams syndrome.
Where Is the GTF2I Gene Located? Cytogenetic Location: 7q11.23 Molecular Location on chromosome 7: base pairs 73,709,965 to 73,812,957
The GTF2I gene is located on the long (q) arm of chromosome 7 at position 11.23. More precisely, the GTF2I gene is located from base pair 73,709,965 to base pair 73,812,957 on chromosome 7.
References These sources were used to develop the Genetics Home Reference gene summary on the GTF2I gene. •
Danoff SK, Taylor HE, Blackshaw S, Desiderio S. TFII-I, a candidate gene for Williams syndrome cognitive profile: parallels between regional expression in mouse brain and human phenotype. Neuroscience. 2004;123(4):931-8. PubMed citation
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Egloff AM, Desiderio S. Identification of phosphorylation sites for Bruton's tyrosine kinase within the transcriptional regulator BAP/TFII-I. J Biol Chem. 2001 Jul 27;276(30):27806-15. Epub 2001 May 23. PubMed citation
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Hirota H, Matsuoka R, Chen XN, Salandanan LS, Lincoln A, Rose FE, Sunahara M, Osawa M, Bellugi U, Korenberg JR. Williams syndrome deficits in visual spatial processing linked to GTF2IRD1 and GTF2I on chromosome 7q11.23. Genet Med. 2003 Jul-Aug;5(4):311-21. PubMed citation
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Morris CA, Mervis CB, Hobart HH, Gregg RG, Bertrand J, Ensing GJ, Sommer A, Moore CA, Hopkin RJ, Spallone PA, Keating MT, Osborne L, Kimberley KW, Stock AD. GTF2I hemizygosity implicated in mental retardation in Williams syndrome: genotype-
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phenotype analysis of five families with deletions in the Williams syndrome region. Am J Med Genet A. 2003 Nov 15;123(1):45-59. PubMed citation •
Perez Jurado LA, Wang YK, Peoples R, Coloma A, Cruces J, Francke U. A duplicated gene in the breakpoint regions of the 7q11.23 Williams-Beuren syndrome deletion encodes the initiator binding protein TFII-I and BAP-135, a phosphorylation target of BTK. Hum Mol Genet. 1998 Mar;7(3):325-34. PubMed citation
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Tassabehji M. Williams-Beuren syndrome: a challenge for genotype-phenotype correlations. Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R229-37. Epub 2003 Sep 2. Review. PubMed citation
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Yang W, Desiderio S. BAP-135, a target for Bruton's tyrosine kinase in response to B cell receptor engagement. Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):604-9. PubMed citation
What Is the Official Name of the GTF2IRD1 Gene?8 The official name of this gene is “GTF2I repeat domain containing 1.” GTF2IRD1 is the gene's official symbol. The GTF2IRD1 gene is also known by other names, listed below.
What Is the Normal Function of the GTF2IRD1 Gene? The GTF2IRD1 gene provides instructions for making a protein that regulates the activity of many other genes. This protein probably interacts with specific regions of DNA and with other proteins to turn genes on or off. Based on this role, the GTF2IRD1 protein is called a transcription factor. Although its exact function is unknown, the GTF2IRD1 gene is active in many of the body's tissues. It appears to be particularly important for gene regulation in the brain and in muscles used for movement (skeletal muscles). Studies suggest that this gene also plays a role in the development of tissues in the bones and face (craniofacial development).
What Conditions Are Related to the GTF2IRD1 Gene? Williams Syndrome - Associated with the GTF2IRD1 Gene The GTF2IRD1 gene is located in a region of chromosome 7 that is deleted in people with Williams syndrome. As a result of this deletion, people with this condition are missing one copy of the GTF2IRD1 gene in each cell. Studies suggest that the loss of this gene may contribute to some of the characteristic features of Williams syndrome, including the distinctive facial features and problems with visual-spatial tasks (such as writing and drawing). Researchers are investigating how a deletion of this gene may be related to these specific features. 8
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/gene=gtf2ird1;jsessionid=03441A5067AE49DD569B8E7A9D34ACCC.
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Williams Syndrome
Where Is the GTF2IRD1 Gene Located? Cytogenetic Location: 7q11.23 Molecular Location on chromosome 7: base pairs 73,506,055 to 73,654,852
The GTF2IRD1 gene is located on the long (q) arm of chromosome 7 at position 11.23. More precisely, the GTF2IRD1 gene is located from base pair 73,506,055 to base pair 73,654,852 on chromosome 7.
References These sources were used to develop the Genetics Home Reference gene summary on the GTF2IRD1 gene. •
Franke Y, Peoples RJ, Francke U. Identification of GTF2IRD1, a putative transcription factor within the Williams-Beuren syndrome deletion at 7q11.23. Cytogenet Cell Genet. 1999;86(3-4):296-304. PubMed citation
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Hirota H, Matsuoka R, Chen XN, Salandanan LS, Lincoln A, Rose FE, Sunahara M, Osawa M, Bellugi U, Korenberg JR. Williams syndrome deficits in visual spatial processing linked to GTF2IRD1 and GTF2I on chromosome 7q11.23. Genet Med. 2003 Jul-Aug;5(4):311-21. PubMed citation
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O'Mahoney JV, Guven KL, Lin J, Joya JE, Robinson CS, Wade RP, Hardeman EC. Identification of a novel slow-muscle-fiber enhancer binding protein, MusTRD1. Mol Cell Biol. 1998 Nov;18(11):6641-52. Erratum in: Mol Cell Biol 2000 Jul;20(14):5361. PubMed citation
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Osborne LR, Campbell T, Daradich A, Scherer SW, Tsui LC. Identification of a putative transcription factor gene (WBSCR11) that is commonly deleted in Williams-Beuren syndrome. Genomics. 1999 Apr 15;57(2):279-84. PubMed citation
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Tassabehji M, Carette M, Wilmot C, Donnai D, Read AP, Metcalfe K. A transcription factor involved in skeletal muscle gene expression is deleted in patients with Williams syndrome. Eur J Hum Genet. 1999 Oct-Nov;7(7):737-47. PubMed citation
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Tassabehji M, Hammond P, Karmiloff-Smith A, Thompson P, Thorgeirsson SS, Durkin ME, Popescu NC, Hutton T, Metcalfe K, Rucka A, Stewart H, Read AP, Maconochie M,
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Donnai D. GTF2IRD1 in craniofacial development of humans and mice. Science. 2005 Nov 18;310(5751):1184-7. Epub 2005 Nov 3. PubMed citation •
Tassabehji M. Williams-Beuren syndrome: a challenge for genotype-phenotype correlations. Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R229-37. Epub 2003 Sep 2. Review. PubMed citation
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Yan X, Zhao X, Qian M, Guo N, Gong X, Zhu X. Characterization and gene structure of a novel retinoblastoma-protein-associated protein similar to the transcription regulator TFII-I. Biochem J. 2000 Feb 1;345 Pt 3:749-57. PubMed citation
What Is the Official Name of the LIMK1 Gene?9 The official name of this gene is “LIM domain kinase 1.” LIMK1 is the gene's official symbol. The LIMK1 gene is also known by other names, listed below.
What Is the Normal Function of the LIMK1 Gene? The LIMK1 gene provides instructions for making a protein that is highly active in the brain, where it is believed to be involved in the development of nerve cells. Researchers suggest that this protein may play an important role in areas of the brain that are responsible for processing visual-spatial information (visuospatial constructive cognition). These parts of the brain are important for visualizing an object as a set of parts and performing tasks such as writing, drawing, constructing models, and assembling puzzles. Within cells, the LIMK1 protein likely regulates aspects of the cytoskeleton, the structural framework that helps to determine cell shape, size, and movement. The LIMK1 protein helps control the organization of actin filaments, which are long, thin fibers that make up a significant part of the cytoskeleton. Actin filaments are necessary for several normal cellular functions, such as cell division, cell movement (motility), maintenance of cell shape, transport of proteins and other molecules within cells, and chemical signaling between cells.
What Conditions Are Related to the LIMK1 Gene? Cancers - Associated with the LIMK1 Gene The LIMK1 protein is produced at unusually high levels (overexpressed) in some cancerous tumors. For example, increased amounts of this protein have been found in a form of skin cancer called melanoma and in cancers of the ovary, lung, breast, and prostate. Researchers believe that high levels of the LIMK1 protein may be associated with changes in the organization of actin filaments and an increased chance that a tumor will invade other tissues.
9
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/gene=limk1.
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Williams Syndrome
Williams Syndrome - Associated with the LIMK1 Gene The LIMK1 protein is produced at unusually high levels (overexpressed) in some cancerous tumors. For example, increased amounts of this protein have been found in a form of skin cancer called melanoma and in cancers of the ovary, lung, breast, and prostate. Researchers believe that high levels of the LIMK1 protein may be associated with changes in the organization of actin filaments and an increased chance that a tumor will invade other tissues.
Where Is the LIMK1 Gene Located? Cytogenetic Location: 7q11.23 Molecular Location on chromosome 7: base pairs 73,136,091 to 73,174,789
The LIMK1 gene is located on the long (q) arm of chromosome 7 at position 11.23. More precisely, the LIMK1 gene is located from base pair 73,136,091 to base pair 73,174,789 on chromosome 7.
References These sources were used to develop the Genetics Home Reference gene summary on the LIMK1 gene. •
Davila M, Frost AR, Grizzle WE, Chakrabarti R. LIM kinase 1 is essential for the invasive growth of prostate epithelial cells: implications in prostate cancer. J Biol Chem. 2003 Sep 19;278(38):36868-75. Epub 2003 Jun 23. PubMed citation
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Gene Review: Williams Syndrome
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Gray V, Karmiloff-Smith A, Funnell E, Tassabehji M. In-depth analysis of spatial cognition in Williams syndrome: A critical assessment of the role of the LIMK1 gene. Neuropsychologia. 2006;44(5):679-85. Epub 2005 Oct 10. PubMed citation
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Hoogenraad CC, Akhmanova A, Galjart N, De Zeeuw CI. LIMK1 and CLIP-115: linking cytoskeletal defects to Williams syndrome. Bioessays. 2004 Feb;26(2):141-50. Review. PubMed citation
Studies
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Meyer-Lindenberg A, Mervis CB, Sarpal D, Koch P, Steele S, Kohn P, Marenco S, Morris CA, Das S, Kippenhan S, Mattay VS, Weinberger DR, Berman KF. Functional, structural, and metabolic abnormalities of the hippocampal formation in Williams syndrome. J Clin Invest. 2005 Jul 1;115(7):1888-1895. Epub 2005 Jun 9. PubMed citation
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Morris CA, Mervis CB. Williams syndrome and related disorders. Annu Rev Genomics Hum Genet. 2000;1:461-84. Review. PubMed citation
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Rosso S, Bollati F, Bisbal M, Peretti D, Sumi T, Nakamura T, Quiroga S, Ferreira A, Caceres A. LIMK1 regulates Golgi dynamics, traffic of Golgi-derived vesicles, and process extension in primary cultured neurons. Mol Biol Cell. 2004 Jul;15(7):3433-49. Epub 2004 Apr 16. PubMed citation
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Stanyon CA, Bernard O. LIM-kinase1. Int J Biochem Cell Biol. 1999 Mar-Apr;31(3-4):38994. Review. PubMed citation
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Tassabehji M. Williams-Beuren syndrome: a challenge for genotype-phenotype correlations. Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R229-37. Epub 2003 Sep 2. Review. PubMed citation
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Yoshioka K, Foletta V, Bernard O, Itoh K. A role for LIM kinase in cancer invasion. Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7247-52. Epub 2003 May 30. PubMed citation
What Is the Official Name of the NCF1 Gene?10 The official name of this gene is “neutrophil cytosolic factor 1, (chronic granulomatous disease, autosomal 1).” NCF1 is the gene's official symbol. The NCF1 gene is also known by other names, listed below.
What Is the Normal Function of the NCF1 Gene? The NCF1 gene provides instructions for making a protein called neutrophil cytosolic factor 1. This protein is one part (subunit) of a larger enzyme complex called NADPH oxidase, which plays an essential role in the immune system. Specifically, NADPH oxidase is active in immune system cells called phagocytes. These cells engulf and destroy foreign invaders such as viruses, bacteria, and fungi. The presence of foreign invaders activates phagocytes and triggers the assembly of NADPH oxidase. This enzyme participates in a chemical reaction that converts oxygen to a toxic molecule called superoxide. Superoxide is used to generate several other compounds, including hydrogen peroxide (a strong disinfectant) and hypochlorous acid (the active ingredient in bleach). These highly reactive, toxic substances are known as reactive oxygen species. Phagocytes use these substances to kill foreign invaders, preventing them from reproducing in the body and causing illness.
10
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/gene=ncf1;jsessionid=03441A5067AE49DD569B8E7A9D34ACCC.
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Williams Syndrome
What Conditions Are Related to the NCF1 Gene? Williams Syndrome - Associated with the NCF1 Gene The NCF1 gene is located in a region of chromosome 7 that is often deleted in people with Williams syndrome. As a result of this deletion, some people with this condition are missing one copy of the NCF1 gene in each cell. Researchers have found that the loss of this gene appears to lower the risk of developing high blood pressure (hypertension). People with only one copy of the NCF1 gene have reduced levels of the neutrophil cytosolic factor 1 protein, which decreases the activity of NADPH oxidase and results in the production of fewer reactive oxygen species. Studies suggest that reactive oxygen species play an important role in blood vessel changes related to hypertension. Other Disorders - Caused by Mutations in the NCF1 Gene The NCF1 gene is located in a region of chromosome 7 that is often deleted in people with Williams syndrome. As a result of this deletion, some people with this condition are missing one copy of the NCF1 gene in each cell. Researchers have found that the loss of this gene appears to lower the risk of developing high blood pressure (hypertension). People with only one copy of the NCF1 gene have reduced levels of the neutrophil cytosolic factor 1 protein, which decreases the activity of NADPH oxidase and results in the production of fewer reactive oxygen species. Studies suggest that reactive oxygen species play an important role in blood vessel changes related to hypertension.
Where Is the NCF1 Gene Located? Cytogenetic Location: 7q11.23 Molecular Location on chromosome 7: base pairs 73,826,244 to 73,841,594
The NCF1 gene is located on the long (q) arm of chromosome 7 at position 11.23. More precisely, the NCF1 gene is located from base pair 73,826,244 to base pair 73,841,594 on chromosome 7.
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References These sources were used to develop the Genetics Home Reference gene summary on the NCF1 gene. •
Babior BM, Lambeth JD, Nauseef W. The neutrophil NADPH oxidase. Arch Biochem Biophys. 2002 Jan 15;397(2):342-4. Review. PubMed citation
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Chanock SJ, Roesler J, Zhan S, Hopkins P, Lee P, Barrett DT, Christensen BL, Curnutte JT, Gorlach A. Genomic structure of the human p47-phox (NCF1) gene. Blood Cells Mol Dis. 2000 Feb;26(1):37-46. PubMed citation
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Del Campo M, Antonell A, Magano LF, Munoz FJ, Flores R, Bayes M, Perez Jurado LA. Hemizygosity at the NCF1 gene in patients with Williams-Beuren syndrome decreases their risk of hypertension. Am J Hum Genet. 2006 Apr;78(4):533-42. Epub 2006 Jan 31. PubMed citation
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Jurkowska M, Bernatowska E, Bal J. Genetic and biochemical background of chronic granulomatous disease. Arch Immunol Ther Exp (Warsz). 2004 Mar-Apr;52(2):113-20. Review. PubMed citation
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Roesler J, Curnutte JT, Rae J, Barrett D, Patino P, Chanock SJ, Goerlach A. Recombination events between the p47-phox gene and its highly homologous pseudogenes are the main cause of autosomal recessive chronic granulomatous disease. Blood. 2000 Mar 15;95(6):2150-6. PubMed citation
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Vazquez N, Lehrnbecher T, Chen R, Christensen BL, Gallin JI, Malech H, Holland S, Zhu S, Chanock SJ. Mutational analysis of patients with p47-phox-deficient chronic granulomatous disease: The significance of recombination events between the p47-phox gene (NCF1) and its highly homologous pseudogenes. Exp Hematol. 2001 Feb;29(2):23443. PubMed citation
Federally Funded Research on Williams Syndrome The U.S. Government supports a variety of research studies relating to Williams syndrome. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.11 CRISP (Computerized Retrieval of Information on Scientific Projects) CRISP is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to Williams syndrome.
11 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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Williams Syndrome
For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore Williams syndrome. The following is typical of the type of information found when searching the CRISP database for Williams syndrome: •
Project Title: AUDITORY MEMORY PROCESSING IN WILLIAMS SYNDROME Principal Investigator & Institution: Marler, Jeffrey A.; Communication Scis & Disorders; James Madison University 800 S Main St Harrisonburg, Va 22807 Timing: Fiscal Year 2004; Project Start 01-JUL-2003; Project End 31-MAY-2007 Summary: (provided by applicant): This project investigates the sensory and memory underpinnings of language processing in individuals with Williams syndrome (WS) and Down's syndrome (DS). Both syndromes are genetically-based neurodevelopmental disorders characterized by an uneven profile of language strengths and weaknesses. In the presence of mild-to-moderate mental retardation, individuals with WS show relative strengths in phonology, verbal short-term memory, and expressive vocabulary. In contrast, individuals with DS show relatively weak phonological abilities, poor verbal short-term memory, and diminished expressive vocabulary. In spite of minimal empirical support, current theories about language function in WS are frequently grounded upon an assumption of relative strengths in auditory processing. First, behavioral auditory measurements are examined including air conduction, tympanometry, otoacoustic emissions, simultaneous and backward masking. These measures are then compared with both (a) physiological responses indexing early auditory memory and (b) phonological analyses indexing early language processing. The inverse pattern of strengths and weaknesses in these two clinical populations provides an opportunity to: (1) empirically examine auditory sensitivity in individuals with WS, (2) empirically test the hypothesis that short-term auditory processing is particularly robust in individuals with WS, and (3) test a current hypothesis that there is a strong correlation between auditory processing, auditory memory, and phonological processing in two groups with confirmed genetic disorders. Important clinical applications are to investigate the possibility of higher-than-expected instances of hearing loss in WS and to identify auditory interactions with language function.
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Project Title: AUTOMATED DETECTION OF GENE DUPLICATIONS OR DELETIONS Principal Investigator & Institution: Merchant, Fatima A.; Lead Research Engineer; Advanced Digital Imaging Research, Llc 2450 S Shore Blvd, Ste 305 League City, Tx 775732997 Timing: Fiscal Year 2005; Project Start 01-APR-2000; Project End 19-MAR-2007 Summary: (provided by applicant): This project will further develop automated instrumentation and image analysis techniques to detect gene duplications or deletions in interphase FISH, which are difficult to detect by routine cytogenetics. There is a growing list of genetic disorders that result from chromosomal anomalies, related to either duplications or deletions. These include: (1) neuropathies; Charcot-Marie-Tooth Disease (CMT1A) and Hereditary Neuropathy with Pressure Palsies (HNPP), (2) neurological disorders; Pelizaeus-Merzbacher Disease (PMD) and X-Linked Spastic Paraplegia (SPG2), (3) muscular wasting disorders; Duchene (DMD) and Becker Muscular Dystrophy (BMD), (4) contiguous-gene syndromes; Smith-Magenis Syndrome (SMS). Our approach is to use readily available DNA probes, followed by automated genetic screening to detect duplications/deletions. We will develop an imaging system for the automated identification of interphase cells, and use sophisticated image analysis
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for high-resolution detection and separation of microscopic rearrangements. In the Phase I project we evaluated the feasibility of newly developed imaging algorithms, for effectively and precisely identifying the separation of FISH dot duplicates. Algorithms were developed for automatically (1) segmenting dots, (2) computing the integrated fluorescence intensity of dots, (3) determining the separation distance, and (4) classifying duplicates and single dots. In Phase II we will incorporate the newly developed imaging algorithms into our automated imaging system, and test the prototype clinically. We will also develop and implement three-dimensional modeling techniques to obtain an unbiased estimate of the spatial distance between duplicated genes. Phase III will commercialize the instrument. Computer automation will make genetic screening practical on a large scale by reducing costs and relieving humans of tedious duties. This approach will be most valuable to medical genetics, particularly for screening CMT1A/HNPP, PMD/SPG2, DMD/BMD, and SMS. Duplications have also been identified for the Prader-Willi /Angelman syndrome region that result in autism. Duplications, such as for 22ql 1.2 and 17pl 1.2 have been described and result in a rather mild phenotype. But duplications of the Williams syndrome region have not been described and thus, the phenotype is unknown. The ability to screen patients for duplications by interphase FISH analysis will likely identify a large number of individuals that would benefit from medical intervention. It may uncover syndromes that previously had no identifiable etiology. This will provide a screening test and eventually a diagnostic test for those individuals with perhaps mild phenotypes, such as learning disabilities. •
Project Title: BAP135 IN THE CENTRAL NERVOUS SYSTEM Principal Investigator & Institution: Danoff, Sonye K.; Environmental Health Sciences; Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680 Timing: Fiscal Year 2005; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: (Applicant's Abstract): This application outlines a training program to be carried out under the mentorship of Dr. Stephen Desiderio in the Department of Molecular Biology and Genetics at the Johns Hopkins University School of Medicine. The applicant's goals are to study the role of a transcription factor, BAP135, in normal neuronal function, as well as to evaluate this gene as a candidate for the neurocognitive phenotype of Williams Syndrome. The training program has been designed to gain expertise in the fields of molecular biology and transcriptional regulation. BAP135 is a recently described transcription factor which appears to define a new family that also includes WBSCR11. BAP135 mRNA is expressed in multiple tissues in mouse, but is most abundant in regions of the central nervous system. Expression of BAP135 is highest during the development of synaptic connections and remains high in areas of ongoing synaptic plasticity. The pattern of BAP135 expression is of further interest as the gene for BAP135 maps to the region of chromosome 7 commonly deleted in the genetic disorder, Williams Syndrome. This syndrome includes a characteristic neurocognitive defect which might be explained by deletion of a transcription factor such as BAP135. Studies are proposed to gain an understanding of how BAP135 functions as a transcriptional activator in neurons. As part of Specific Aim 1, the cellular and subcellular localization of BAP135 protein with development will be established. This will also address the patterns of expression of the four isoforms of BAP135 known to exist. Several aspects of the induction of BAP135 transcriptional activation will be addressed in Specific Aim 2. Both DNA binding of BAP135 and transactivation of reporter constructs in neurons will be evaluated and the effect of pathways involved in synaptic plasticity on these functions will be addressed. Specific Aim 3 focuses on the pathway downstream of BAP135 in neurons. Genes modulated by BAP135 activity will
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Williams Syndrome
be investigated using DNA expression arrays. Finally, in Specific Aim 4, lymphoblast lines from patients with Williams Syndrome will be examined for deletions and mutations in the BAP135 locus. Mutations identified will be evaluated for effects on DNA binding and transactivation by BAP135 in neurons. •
Project Title: BRAIN CYTOARCHITECTONIC WILLIAMS SYNDROME
CHARACTERIZATION
OF
Principal Investigator & Institution: Galaburda, Albert M.; Professor; Salk Institute for Biological Studies 10010 N Torrey Pines Rd La Jolla, Ca 920371099 Timing: Fiscal Year 2005 Summary: We are requesting continuing support to study anatomical links between genes and behavior in Williams I Syndrome (WS). The present period of research will continue to refine the testing of hypotheses that have emerged from the synthesis of collective results from the previous period across Projects I-V. The overarching hypothesis stemming from the neurocognitive, anatomical and imaging, neurophysiological, andl genetic findings in WS implicates a disordered establishment of dorsoventral and anteroposterior gradients during the formation of cerebral cortex. The specific hypothesis is that the dorsal caudal cortex is set up and functions abnormally as a direct result of some of the deleted genes, and that ventral and anterior cortices change anatomically and functionally because of it. Thus far anatomical research showed curtailment of the dorsal central sulcus and reduction in dorsocaudal forebrain. At the architectonic level, cell measurements indicated alterations both in dorsal and ventral posterior cortices, but of different types, which is congruenl with neuroimaging results showing curtailement of caudodorsal areas and relative enlargement of frontal and ventral areas. A unique partial deletion case led us to study transcription factors GTF21 and GTF21rd staining in visual cortex, which showed abnormalities in cortex related to the dorsal visual pathway. The specific aims of this component of the Program Project relate to the overarching hypothesis: Thus, we will compare dorsal and ventral cortices caudally and frontally. A corollary hypothesis claims that abnormalities in dorsocaudal brain means that other spatially related cortices, in addition to the spatial visual cortex, will be found to be abnormal. A second corollary is that the abnormal affiliative behavior in WS is related to enhanced development of ventral anterior regions, including the amygdala, the lateral hypothalamus, and relevant frontomedial cortex, which will be one aim in this study, too. Finally, two subcortical nuclei, the LGN and the MGN will be studied with respect to the hypothesis that magnocellular subsystems within these nuclei relate differentially to the dorsocaudal and ventrocaudal cortex. A major aim of the proposed research will be to provide information that will inform research carried out in the behavioral, neurophysiological, imaging, and genetic components of the program project, as well as deriving clues from findings in those project to help guide our research in the present project. The collaboration, thus far, has been productive to a greater degree than the sum of its parts. •
Project Title: CENTER FOR THE NEURAL BASIS OF LANGUAGE AND LEARNING Principal Investigator & Institution: Trauner, Doris A.; Professor and Vice-Chairman; Ctr for Research in Language; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2005; Project Start 16-SEP-1985; Project End 31-JUL-2007
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Summary: The purpose of this multi-disciplinary Center is to explore the neural bases of language and cognitive development from 7-18 years of age, combining cross-sectional and longitudinal behavioral methods with neural imaging (event-related brain potentials (ERP); functional magnetic resonance imaging (fMRI) to study normal and abnormal brain development, and the alternative forms of brain organization that can emerge under pathological conditions, and the alternative forms of brain organization that can emerge under pathological conditions. Project A focuses on children with Language Impairment (LI); it examines the cognitive and neural correlates of LI, and test competing hypotheses about the processing deficits that underlie this disorder. Project B follows children with focal lesions (FL) to one side of the brain, acquired pre- or perinatally (before 6 months of ages); it will provide behavioral, fMRI and ERP evidence regarding the alternative forms of organization the underlie plastic reorganization in the plastic reorganization in this population. Project C compares Williams Syndrome (WMS), a rare form of mental retardation in which language is especially vulnerable. Project D is new, and constitutes an extension of Project 2 to study children with lesions of later onset in childhood, children with bilateral pathology, and children with slowly evolving lesions due to tumor; the purpose of this project is to increase our understanding of developmental and neurological limits on plasticity. Project E is new, a groundbreaking series of studies using fMRI, including BOLD activation studies of language, spatial processing and spatial attention, as well as perfusion studies of vascular organization. Project F continues our ERP studies of language, spatial cognition and basic auditory-visual processing in all populations. Core A handles administration, data base management, tracking and statistical consultation. Core B is responsible for recruitment of controls, and handles screening, diagnosis and induction of all populations. Core C is a new joint behavioral testing facility that handles language and behavioral testing (excluding ERP and fMRI) for all populations, including language transcription. •
Project Title: COGNITIVE-BRAIN PHENOTYPING OF ATYPICAL CHINESE CHILDREN Principal Investigator & Institution: Karmiloff-Smith, Annette; U of L University College London London, Wc1e 6Bt Timing: Fiscal Year 2005; Project Start 28-SEP-2003; Project End 28-FEB-2006 Summary: (provided by applicant): The present proposal describes a series of planning activities to develop an international collaborative program of research on cognitive and brain phenotypes of mentally retarded Chinese children with genetic disorders. Specifically, an international team of medical, psychological, genetic, and computational researchers from P.R. China, the United Kingdom, the United States, and Canada will collaborate to study Chinese children with Fragile-X syndrome (FXS), Williams syndrome (WS), and Down syndrome (DS). The specific aims of the present research planning proposal are:(1) To assess the existing research infrastructure at the Chinese institution (Zhejiang University) for conducting the proposed research activities, (2) To enhance the research capacities of our Chinese research team through workshops and short-term training; (3) To conduct pilot studies that (a) test the feasibility of a computer-assisted 3D photography-based system for identifying a large population of mentally retarded children whose facial dysmorphology may suggest FXS, WS or DS and verify such identifications by genetic tests, (b) translate, adapt, and pilot-test procedures developed by the researchers in UK, US, and Canada to assess children with genetic disorders in terms of their abilities in the areas of language, executive function, and faces and visual-spatial information processing, and compare the Chinese children's cognitive profiles with the existing profiles of affected Western children; (c) use event-
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related potential techniques to examine the neuro-physiological correlates of a small group of the Chinese children with WS, FXS, and DS when they process language and face-spatial information, and compare the results with those obtained with the existing samples of affected Western children. Based on the outcome of 1,2, and 3, the international interdisciplinary team will develop a R01 research proposal that will systematically examine cognitive and brain functions or dysfunctions of Chinese children with Williams, Fragile-X, and Down syndromes from infancy to middle childhood. Our long-term goal is to chart the developmental trajectories of cognitive and brain development in children with genetic disorders, to understand the interaction between genetic abnormality and neuro-cognitive development in different sociocultural contexts, and to provide information for the creation of syndrome-specific and, if necessary, culture-specific intervention programs. •
Project Title: DEVELOPMENT OF FACE PERCEPTION AND RECOGNITION Principal Investigator & Institution: Grill-Spector, Kalanit; Psychology; Stanford University 1215 Welch Road, Mod B Stanford, Ca 943055402 Timing: Fiscal Year 2006; Project Start 01-SEP-2006; Project End 31-AUG-2008 Summary: (provided by applicant): Face recognition is crucial for social interaction and development, and undergoes a prolonged maturation until the teens. However, little is known about the maturation of the normal psychological or neural processes that support the development of face perception in children. The goal of this proposal is to use cutting-edge psychophysical and neuroscience methods to elucidate the development of psychological processes involved in face recognition, the underlying neural systems, and their link. Such a rigorous and convergent approach in elucidating normal development is crucial for understanding the many developmental disorders that involve deficits in visual or face processing such as Williams Syndrome, autism and congenital prosopagnosia. Recent psychophysical studies found that face recognition in adults involves multiple stages of processing, including visual categorization (face versus non face) and individual identification (e.g., George versus Bill). Imaging studies revealed that in adults, specific face selective regions in the visual cortex, such as the fusiform "face area" (FFA) are also involved in the categorization and identification of faces. Our preliminary data indicate that the FFA is substantially smaller in children (7-11) compared to adults, correlating with their lower levels of face recognition memory. These data suggest a striking and prolonged maturation of face processing and its neural substrates. However, it is not known how this maturation relates to specific stages of face processing, and whether this maturation is specific to the FFA, or involves the visual cortex more generally. We hypothesize that development of face processing specifically involves maturation of the FFA. Therefore, we propose to examine the links between maturation of the FFA and face perception. We will determine: (1) which behavioral aspects of face processing mature after age 7, using psychophysics; (2) whether the maturation of the FFA occurs in tandem with (or lags) maturation of early and/or higher order visual cortex, using standard fMRI; (3) whether the (smaller) FFA in children is involved in face (or object) categorization and identification, using a combination of psychophysics and standard fMRI and (4) whether maturation of FFA involves increases in face selectivity and/or fine-scale structures within the FFA, using high resolution fMRI. We expect our results to address wide gaps in our understanding of normal visual development, add significant knowledge to theories of face perception and object representation, and provide an essential base for future research on developmental disorders and pediatric imaging in general.
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Project Title: DEVELOPMENT OF MEDIAL TEMPORAL LOBE FUNCTIONS Principal Investigator & Institution: Bachevalier, Jocelyne H.; Professor; None; Emory University 1784 North Decatur Road, Suite 510 Atlanta, Ga 30322 Timing: Fiscal Year 2005; Project Start 01-AUG-1998; Project End 30-JUN-2010 Summary: (provided by applicant): Early dysfunction of medial temporal lobe (MTL) structures is associated with many developmental mental disorders in humans, such as schizophrenia, autism, Williams syndrome. These disorders of unknown origin have significant impact on the normal cognitive development of a young individual, resulting in severe disabilities in the realms of perception, memory, language, thinking, experience of emotions, and social intelligence that span the entire life of an individual. Given the paucity of information in primates, regarding the normal anatomical and functional maturation of MTL structures and the long-term consequences of early damage to this region, the goal of our research program is to follow the anatomical and functional development of specific structures within this region, and compare and contrast the long-term behavioral and neuroanatomical effects of early vs late damage to this region. The overall hypothesis to be tested is whether early damage to the medial temporal lobe region yields the same behavioral changes, and anatomical and chemical re-organization than those seen after similar damage in adulthood. The specific aims of the present application are (1) to continue our investigation of the role of hippocampal formation (HF) and perirhinal cortex (PRh) in the development of memory processes, (2) to compare and contrast the effects of early damage to these 2 structures on behavioral responses and cognitive processes, such as memory, emotional reactivity, social skills, and reward assessment, and (3) to study the anatomical and chemical re-organization of brain connections that follows the early hippocampal and perirhinal lesions. These behavioral studies will be performed in infant monkeys with neonatal selective HF and PRh lesions, and controls tested in behavioral tasks designed to measure memory, emotions, and social skills. These studies will provide insights into the pathophysiology and etiology of devastating developmental human disorders and primate model of extreme value for the development of new therapies.
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Project Title: DEVELOPMENT OF MOTION PROCESSING IN HUMAN INFANTS Principal Investigator & Institution: Dobkins, Karen R.; Professor; Psychology; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2005; Project Start 01-MAR-1998; Project End 31-MAR-2008 Summary: (provided by applicant): The ability to perceive visual motion is one of the most fundamental and essential facets of vision. While much has been learned over the years about the psychophysics and neurophysiology of motion processing in adults, little is known about its development in infants. The long-term objective of this research is to characterize the development of visual motion perception in human infants, and to understand how underlying neural mechanisms can account for the progression from an immature to an adult-like state. To this end, visual psychophysical experiments are conducted in infants 1-5 months of age, and the results are modeled in terms of known or hypothetical neural mechanisms. Data are collected from infants using simple observational techniques that rely on the fact that infants preferentially stare at a patterned stimulus rather than a blank field and that infants exhibit directionally appropriate eye movements in response to moving targets. Together, we use these techniques to ask questions regarding the development of: (1) direction and speed discrimination; (2) motion integration across visual space; (3) chromatic (red/green) input to motion processing; and 4) contextual effects on motion processing. The study of infant motion processing is particularly appealing as much is known about the neural
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basis of motion processing in adults. Thus, discovering the time course of development for different aspects of motion processing will improve our understanding of the neural development of specific visual areas known to be involved in motion processing. From the clinical standpoint, assessment of motion processing capacities could potentially be used to diagnose damage to motion processing areas during development. For example, there is recent evidence that dyslexia (e.g., Livingstone et al., 1991; Galaburda & Livingstone, 1993; Demb et al., 1997; 1998), autism (Spencer, et al., 2000; Gepner & Mestre, 2002; Blake et al., 2003) and Williams Syndrome (Atkinson et al., 1997) are associated with damage to motion-related areas of the brain. In virtue of such findings, it is quite possible that early detection of these disorders could be aided by simple tests of motion processing capabilities. Thus, assessment of the normal development of visual functions, such as motion processing, is likely to play an important role in clinical diagnosis and in monitoring the effects of treatment in infants and children with visual disabilities. •
Project Title: DIAGNOSTIC METHODS AND SERVICES Principal Investigator & Institution: Rose, Fredric; Salk Institute for Biological Studies 10010 N Torrey Pines Rd La Jolla, Ca 920371099 Timing: Fiscal Year 2005 Summary: The Core is responsible for the identification, diagnostic clarification, induction, scheduling, and tracking of all I participants in the Program Project. The Core also coordinates the collection of data during induction, entry of these data into the Program Project Database and Data Archives, and the tracking of data acquisition and analyses across all projects. The Core is organized into a set of service-based subcores to provide cost-efficient and centralized resource services to the five Projects. These subcores will function as follows: (1) Outreach and Induction Screening screens all subjects inducted into the Program Project, as well as gathers relevant medical, behavioral, and background information. (2) Behavioral Diagnostics is responsible for diagnostic clarification of our clinical populations during induction, including the application of inclusionary/exclusionary criteria. Additionally, the Core administers the Diagnostic Battery used for control group matching. (3) Molecular Genetics acquires blood samples and relevant donor information from all WS subjects and their parents, and ensure timely delivery to Project I for processing and analysis. (4) Neurophysiology schedules and coordinates the acquisition of ERP data for stet. (5) Functional Neuroanatomy coordinates subject participation in fMRI studies and facilitates data acquisition for Project III. (6) Cellular and Molecular Architectonics initiates postmortem tissue acquisition including brain fixation, MRI, and transportation of the brain to Project IV for analysis. (7) Neurocognitive coordinates the administration of the Basic Neurocognitive Battery in Project I, scores all tests administered, and enters all data into the Program Project database. (8) Subject Tracking and Data Processing is responsible for organizing an efficient schedule of subject interaction within the Program Project, allowing for the collection of all necessary data. This subcore also tracks data after collection and processing to ensure timely and accurate entry to the Project Database, provides data summaries, and ensures an efficient flow of data and information among Projects and Cores.
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Project Title: EARLY DEVELOPMENT WITH WILLIAMS OR DOWN SYNDROME Principal Investigator & Institution: Mervis, Carolyn B.; Professor; Psychological and Brain Sciences; University of Louisville Office of Grants Management Louisville, Ky 40292
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Timing: Fiscal Year 2005; Project Start 15-SEP-2004; Project End 31-JUL-2009 Summary: (provided by applicant): The overall objective of the proposed research is to delineate, and make sense of, the process of lexical development and its relations to communicative development, grammatical development, and both general and specific aspects of nonlinguistic cognitive development. The research will focus on the language and cognitive development of three groups: children with Williams syndrome, children with Down syndrome, and typically developing children. Out research during the current grant period indicates that the language skills of children with Williams syndrome are more advanced than their nonverbal cognitive skills; children with Down syndrome show the opposite pattern. Children who are typically developing tend to have equivalent levels of language and cognitive skills. Because of these differences in the general nature of the relations between language and nonlinguistic cognition, inclusion of all three groups in the same studies provides a unique opportunity to identify factors that are universal and necessary to lexical, communicative, or grammatical development versus those that are specific to particular rates or paths to language acquisitions. The proposed research consists of a 5-year longitudinal study beginning in late infancy and both longitudinal and cross-sectional studies involving preschool-and school-age children. Both observational and experimental methods will be used. There are four specific aims. The first is to delineate the nature of early lexical growth curves. The second is to further examine the role of lexical operating principles (heuristics) and foundational social cognitive abilities in the acquisition and extension of new words. The third is to begin to delineate the development of communicative abilities by toddlers and young children who have Williams syndrome. The fourth is to determine longitudinally the developmental trajectories of language and cognitive abilities for children with Williams syndrome. The research will have implications both for theoretical models of the relations between language and cognition and for the design of cognitive and language intervention strategies for children with developmental disabilities. •
Project Title: FUNCTION OF GENES IN WILLIAMS SYNDROME DELETION REGION Principal Investigator & Institution: Francke, Uta; Professor; Genetics; Stanford University 1215 Welch Road, Mod B Stanford, Ca 943055402 Timing: Fiscal Year 2005; Project Start 01-JUL-2001; Project End 31-MAY-2007 Summary: (provided by applicant): With the Human Genome Project promising to provide a catalog of all human genes in the near future, the main challenge of research in the next century is that of functional genomics. The processes that control gene activation and repression in a developmental-stage and cell-type specific manner are fundamental to understanding normal development and discovering the causes of human disease. Spontaneously recurring microdeletions are ideal for a systematic study of the downstream effects of hemizygosity for the defined set of genes in the deletion. Williams-Beuren syndrome (WBS), a neurodevelopmental disorder with a distinct profile of cognitive and behavioral features serves as a model system to study the genetic and molecular basis of cognition, speech, language, and visuo-spatial processing. WBS is caused by recurrent uniform deletions of 1.6 Mb of DNA from chromosome 7q11.23, that arise by inter- or intrachromosomal recombination between flanking duplicated regions. Within the deletion, 16 genes have been identified and characterized. They function as transcription factors, in DNA replication, chromatin assembly, translation, signal transduction and as structural proteins. Only one, the elastin gene has been linked to a specific manifestation, supravalvular aortic stenosis. To
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evaluate the functional consequences of hemizygosity for the other genes, humans with partial deletions will be identified and mouse models generated with corresponding deletions in the conserved syntenic region on mouse chromosome 5. Target genes of transcription factors and signaling molecules will be identified by microarray studies, comparing gene expression patterns in various tissues from affected humans and deletion mice. Development of a molecular phenotype of WBS links cognitive neuroscience to molecular genetics. Insights gained into the molecular pathways, that lead from the chromosomal deletion to the specific cognitive, behavioral and learning disabilities may have relevance for common developmental disorders, such as attention deficit/hyperactivity disorder and autism, as well as for understanding normal developmental processes. •
Project Title: FUNCTIONAL NEUROANATOMY OF WILLIAMS SYNDROME Principal Investigator & Institution: Reiss, Allan L.; Professor; Salk Institute for Biological Studies 10010 N Torrey Pines Rd La Jolla, Ca 920371099 Timing: Fiscal Year 2005 Summary: During the present grant period, Project III has contributed significantly to this innovative interdisciplinary program project by using advanced, multifaceted imaging methods to further elucidate the "Functional Neuroanatomy of Williams Syndrome". For example, prominent volume reductions in the occipital lobe, accompanied by fMRI studies showing reduced activation within areas comprising primary and secondary visual cortex constitute strong candidates for explaining the neural basis of visual-perceptual deficits in this disorder. As consistent with the longstanding history of Williams syndrome as a genetic syndrome with an identifiable social-emotional phenotype, our data also reinforce the notion of an aberrant emotion system in this disorder. In particular, data from our volumetric, voxel-based morphometric and fMRI analyses suggest that brain areas comprising or associated with the limbic system are preserved, disproportionately large, show greater gray matter density and/or are over-activated in Williams syndrome (e.g., amygdala, hippocampus, anterior cingulate, superior temporal gyrus, insular cortex). In the next project period, we plan to more specifically characterize the WS neurofunctional phenotype using highfield (3T) structural, functional and diffusion tensor magnetic resonance imaging (MRI), advanced analytical methods including new 3-D cortical and subcortical mapping and shape analyses, and recruitment of key comparison groups. These imaging analyses will directly address the brain basis of the fascinating cognitive profile associated with WS, in particular as pertaining to the neural basis of visual and emotion processing. Results from Project III will be highly relevant to the multi-level interdisciplinary research approach characterizing this program project. In particular, we propose direct linkages to the neuropsychological and behavioral data collected in Project I, electrophysiological (ERP) information derived from Project II, neuroanatomical data from Project IV, and molecular genetic analyses from Projects V. Projects V.
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Project Title: PHENOTYPE
GENETICS
OF
TURNER
SYNDROME
NEUROCOGNITIVE
Principal Investigator & Institution: Zinn, Andrew R.; Assistant Professor of Internal Medicine; Internal Medicine; University of Texas Sw Med Ctr/Dallas 5323 Harry Hines Blvd. Dallas, Tx 753909105 Timing: Fiscal Year 2005; Project Start 01-MAR-1997; Project End 31-JUL-2007 Summary: (provided by applicant): Turner syndrome (TS) is a human genetic disorder involving females who lack all or part of one X chromosome. Classic TS features include
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short stature, infertility, and anatomic abnormalities. More recently, characteristic neurocognitive deficits in nonverbal domains such as visual-spatial abilities have been recognized as part of the syndrome. Our original grant proposed to map loci responsible for specific TS cognitive and physical features by collecting a large number of subjects with heterogeneous X chromosome deletions, mapping the deletions using molecular methods, and thoroughly analyzing associated phenotypes. Rigorous statistical analysis showed that deletions of certain regions of the short arm of the X chromosome were associated with specific TS phenotypes, including neurocognitive deficits, short stature, and ovarian failure. Cognitive and physical aspects of the phenotype were dissociable. We narrowed the location of gene(s) responsible for a major component of the TS neurocognitive phenotype to an interval of the distal short arm (Xp) spanning only ~1% of the X chromosome. This same interval has been previously shown to contain a gene termed SHOX, deletions or mutations of which cause short stature and other TS skeletal abnormalities. Following the paradigm of Williams syndrome, another complex genetic disorder with characteristic physical and cognitive phenotypes, we reasoned that TS represents a genetic and phenotypic continuum associated with X chromosome deletions. Furthermore, physical phenotypes associated with SHOX deletions could be used to ascertain a population of subjects with small distal Xp deletions in and around the TS neurocognitive critical region without bias with regard to their neurocognitive phenotypes. Fine-mapping these subjects' deletions will allow us to narrow the TS neurocognitive critical region to a specific gene(s). Furthermore, characterizing the neurocognitive profile of subjects with SHOX point mutations or distal Xp deletions limited just to SHOX will allow us to critically test whether this known TS gene also plays a role in the neurocognitive phenotype. The proposed study takes advantage of our existing clinical collaborations as well as large referral populations for SHOXassociated disorders in Dallas and Philadelphia to obtain a sufficient sample size of unrelated distal Xp deletion subjects for rigorous statistical analyses. The project will combine molecular characterization of subjects with detailed cognitive evaluations to elucidate the role of SHOX or other pseudoautosomal gene deficiencies in the TS neurocognitive phenotype. •
Project Title: IDENTIFICATION OF PERICENTROMERIC IMBALANCES Principal Investigator & Institution: Shaffer, Lisa; Research Professor; School of Biological Sciences; Washington State University 423 Neill Hall Pullman, Wa 99164 Timing: Fiscal Year 2005; Project Start 15-JUL-2004; Project End 30-JUN-2007 Summary: (provided by applicant): Abnormal karyotypes occur in approximately 0.3% of all newborn infants. Of these, interstitial deletions are likely to be a substantial cause of the imbalance. Based on a literature review of deletions and duplications of the human chromosomes that resulted in malformation, it appears that any region of the genome may be subject to rearrangement, but certain parts of the genome are more susceptible than others. Among these are the pericentromeric regions of chromosomes, which seem to be more susceptible to deletion than other internal segments of the chromosome arms. Much effort has gone into the development of telomere-regionspecific probe sets. These sets have uncovered genetic imbalance in 7-23% of cases studied. No effort has been put forth to develop pericentromeric FISH probes. Known deletion syndromes exist close to the centromeres (e.g., Williams syndrome, PotockiShaffer syndrome, DiGeorge syndromes). This project proposes to identify new regions of chromosome imbalance of the pericentromeric regions through the following specific aims: 1) Construct a comparative genome hybridization (CGH) microarray (array CGH) for the pericentromeric regions of all human autosomes and the X chromosome; and 2) detect microdeletions and microduplications (deletions and duplications, respectively,
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too small to be viewed under a microscope) in the pericentromeric regions in a population of patients with mental retardation. Array CGH of the pericentromeric regions will uncover chromosome imbalances in regions of the genome currently not well interrogated with conventional cytogenetics or fluorescence in situ hybridization (FISH). Array CGH provides a platform for efficiently screening the pericentromeric regions of all chromosomes to uncover novel imbalances. It is likely that a substantial proportion of patients with mental retardation have microdeletions (and perhaps the reciprocal microduplications) of the pericentromeric regions of the genome, not detectable with any current FISH probe set. The identification of deletions or duplications in the pericentromeric regions may delineate new syndromes or uncover the etiology of established syndromes. •
Project Title: IMPROVED METHODS FOR SINGLE SUBJECT FMRI ANALYSIS Principal Investigator & Institution: Mazaika, Paul K.; Psychiatry and Behavioral Sci; Stanford University 1215 Welch Road, Mod B Stanford, Ca 943055402 Timing: Fiscal Year 2006; Project Start 01-JUN-2006; Project End 31-MAY-2011 Summary: (provided by applicant): Mental illness is a great burden for the affected individual and economically costly for society. The annual cost of mental disorders has been estimated to be $150 billion, increasing every year, and this total does not include more than three million people receiving disability benefits due to mental disorders. It is imperative that we prioritize research efforts focused on understanding brain function in order to improve diagnostic strategies and discover more effective therapies. Functional Magnetic Resonance Imaging (fMRI) is a powerful tool to visualize and measure typical and atypical cognitive processing. However, many important cognitive processing systems, such as those associated with memory, language, emotion and executive control, only produce small BOLD signals and thus measurements are noisy and have low statistical confidence. Hence, fMRI has not been readily adopted for clinical diagnosis of individual patients. I propose to develop greatly improved methods to suppress the noise sources in fMRI data in order to transform fMRI from a research tool about populations to a consistent and accurate diagnostic tool to study individual cognitive functions. Using the strategy that every noise suppression algorithm must perform well to reliably detect single trial fMRI BOLD signals, I developed visualization methods to "see" deeply into fMRI data to evaluate the quality of the data at every step of fMRI data processing. The preliminary studies indicate that there are clear opportunities to improve fMRI image analysis techniques. The proposed research will first develop and test methods to improve suppression of errors from motion and physiological fluctuations. Then it will translate this research by combining these techniques with pattern recognition to characterize individual cognitive activation patterns in typical and atypical populations. My quantitative science expertise is in image processing, algorithm design, and pattern recognition. The research directly supports my interdisciplinary career development with hands-on experience in experiment planning, fMRI scanner operation, neuroscience coursework, and new software methods for application to severely brain disordered populations. In particular, the subjects for this research will include important clinical psychiatric populations with disorders such as fragile X syndrome, Turner syndrome, autism, Williams syndrome, depression, and bipolar disorder, so that all newly developed methods can be immediately put into practice.
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Project Title: MECHANISTIC PROBLEMS IN EUKARYOTIC GENE REGULATION Principal Investigator & Institution: Widom, Jonathan; Professor and Chair; Biochem/Molecular & Cell Biol; Northwestern University Evanston, Il 602081110 Timing: Fiscal Year 2006; Project Start 01-AUG-1997; Project End 31-MAR-2010 Summary: (provided by applicant): The long-term aim of my research program is to develop a quantitative understanding of gene regulation in vivo. This project focuses on the earliest steps in gene regulation, namely, how gene regulatory proteins gain access to their DMA target sites in chromatin. Access to target sites inside nucleosomes can occur spontaneously, and can be catalyzed by ATP-dependent nucleosome remodeling factors. We are studying both of these mechanisms. Studies in Aim 1 will characterize the spontaneous invasion of nucleosomes by site-specific DMA binding proteins. We will investigate the kinetics for spontaneous access at interior sites in nucleosomes, the effects of higher order chromatin folding on site accessibility, and the rules governing cooperative binding to nucleosomes. Studies in Aim 2 will address how the Drosophila ISWI/Acf1 nucleosome remodeling machine functions as a machine to catalyze and drive the movement of nucleosomes from one position on DNA to another. We will characterize the protein domain organization of this machine, and the interactions between parts of the machine with each other, and between the machine and the ATP and chromatin substrates. We will characterize how the machine changes conformation through a catalytic cycle, and the changes that the machine induces in nucleosomes. Finally, structural changes taking place within the machine throughout a catalytic cycle will be correlated in time, with those in the nucleosome, to develop a detailed picture of the functioning of this broad class of machine. Relevance: The proper regulation of genes is essential for the development and health of all organisms. Understanding how regulatory proteins find and bind to their DNA target sites will lead, over the long term, to new diagnostics and therapeutics. Studies of ATP-dependent nucleosome remodeling factors have a specific relevance to human development and health, as mutations in these factors are responsible for a wide range of human developmental diseases and cancers, including: Williams syndrome, Schimke immunoosseous dysplasia, Cockayne syndrome, X-linked a thalassaemia, mental retardation, malignant rhabdoid tumors, chronic myeloid leukemia, and prostate and lung carcinomas.
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Project Title: MOLECULAR REARRANGEMENTS
ANALYSIS
OF
HUMAN
SUBTELOMERIC
Principal Investigator & Institution: Krantz, Ian D.; Children's Hospital of Philadelphia Joseph Stokes, Jr. Research Institute Philadelphia, Pa 191044318 Timing: Fiscal Year 2005 Summary: Congenital heart disease affects approximately 1% of infants, with an incidence estimated at close to ten times that level among stillbirths. Heart defects are seen both as isolated findings and components of syndromes. Several chromosomal syndromes include heart defects as consistent parts of the phenotype. Examples of such syndromes include Down syndrome (AV canal defects), DiGeorge/velocardiofacial (conotruncal defects), Williams syndrome (supravalvular aortic stenosis, pulmonary vascular involvement), and Alagille syndrome (pulmonary artery defects). Identifying the specific genes involved in these and other complex developmental disorders have contributed to our understanding of the molecular processes involved in cardiac development. Human telomeres and subtelomeres have a unique structure consisting of multiple classes of DNA sequence repeats, as well as single copy sequences. These unique sequence regions are highly gene rich and prone to breakage and rearrangement. Consequences of this chromosome breakage have been shown to result in human
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disease. The development of molecular probe sets that permit the analysis of the integrity of the subtelomeric regions using fluorescence in situ hybridization (FISH) technology has recently advanced the clinical diagnosis of patients with these types of chromosomal rearrangements. Through the use of this testing we have identified over 40 cases of subtelomeric rearrangements. Twenty-five percent of these individuals have congenital heart defects. We have begun to molecularly characterize the deletion boundaries in those cases with a consistent finding of congenital heart defects (specifically chromosome 6p associated with atrial septal defects and pulmonary artery abnormalities, and 9q associated with conotruncal defects). We propose to study a cohort of patients with subtelomeric rearrangements and congenital heart defects, characterize their deletion boundaries, and identify genes within these deletions that are responsible for cardiac defects when mutated. We hypothesize that these studies will lead to the identification of genes responsible for normal cardiac development that when mutated will be responsible for both syndromic and isolated forms of congenital heart defects. •
Project Title: MOLECULAR ANALYSIS OF WILLIAMS SYNDROME Principal Investigator & Institution: Roy, Ananda L.; Associate Professor; Pathology; Tufts University Boston 136 Harrison Avenue Boston, Ma 02111 Timing: Fiscal Year 2005; Project Start 01-JUL-2004; Project End 30-APR-2008 Summary: (provided by applicant): Williams-Beuren Syndrome (WBS) is a neurodevelopmental disorder with multisystem manifestations, including supravalvar aortic stenosis (SVAS), hypercalcemia in infancy, mild to moderate mental retardation, cognitive defects and characteristic craniofacial features. The frequency of this genetic haploinsufficiency is estimated to be 1 in 20,000 live births. WBS is caused by a hemizygous microdeletion of approximately 1.5 MB, spanning 17 genes at chromosomal location 7q11.23. Despite these observations, we lack a complete understanding of molecular basis for this disorder. Although this multisystem dysfunction with unusual craniofacial, behavioral and cognitive features occurs most likely due to haploinsufficiency of several genes, rare cases with much smaller deletions have provided clues to identifying specific genes that may be causal to distinctive physical and cognitive defects. Two of these genes, GTF21 and GTF3 encode the TFII-I family of transcription factors. TFII-I and its relative MusTRD1/BEN exhibit extensive and overlapping expression patterns in a variety of tissues during mouse pre- and postimplantation development, suggesting a functional role for these proteins in early development. These proteins are also abundantly expressed in the hippocampus, a portion of the brain that plays a role in learning and memory, further indicating that they may be causal to some WBS traits. While much has been learned about the TFII-I's mechanism of action, relatively little is known about how MusTRD1/BEN functions. To better understand the molecular basis for WBS, we propose to dissect the functional role of MusTRD1/BEN. We will proceed to analyze the physical and functional interactions of MusTRD1/BEN with Smad factors, which are critical for a variety of developmental processes. Finally, we will employ RNAi technologies to determine the biological role of this factor in osteoblast differentiation.
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Project Title: MOLECULAR GENETIC BASIS OF WILLIAMS SYNDROME Principal Investigator & Institution: Ruddle, Frank H.; Professor of Biology and Human Genetics; Molecular and Cellular Physio; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2005; Project Start 01-JUN-2002; Project End 31-MAY-2007
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Summary: (provided by the applicant): Williams Syndrome (WS) is an autosomal dominant genetic condition characterized by an ensemble of physical, cognitive, and behavioral traits. The syndrome has been mapped to 7ql1.23, where genetic causation is attributed to a microdeletion of approximately 1.5 Mb in length. To date, 17 genes have been identified in the haplo-insufficiency region, which serve as specific candidates for the multiple features of the condition. While the 1.5 Mb deletion occurs most commonly, smaller more informative deletions occur at a lower frequency and facilitate the presumptive identification of genes that are causal to specific cranio-facial and neurological attributes of WS. Currently, deletion mapping implicates genes near the telomeric terminus of the deletion, as most critical in phenotype causation. Three genes are viable candidates. These are CLIP-115, BEN, and TFII-I. CLIP-115 is a cytoplasmic linker protein, while TFII-I and BEN are closely related helix-loop-helix transcription factors. We have recently isolated the BEN gene in mice in a search for factors that bind to the early enhancer of the developmentally important Hoxc8 gene. This implicates BEN and TFII-I as candidate developmental factors, deficiencies of which may be expected to generate the symptomology of WS. In an effort to establish the molecular basis of WS, we will use chromosome engineering and other transgenic methodologies to simulate a haplo-insufficiency for these three candidate genes in mice. The mutant mice will be examined for physical, biochemical, and behavioral phenotypes that are typical of persons with WS. In this way, we hope to implicate definitively the three candidate genes singly or in combination as casual factors in WS. This will represent the first step in establishing the molecular genetic basis of WS. The second step will involve the discovery of downstream genes regulated by the transcription factors BEN and TFIII. We believe certain genes in this category may be profoundly deregulated in the WS haplo-insuficiency condition, and are therefore most probably the immediate causal factors in WS. The establishment of the developmental genetic basis of WS is important beyond the understanding it brings to WS itself. The identification of genes that regulate behavior allows further investigation of genetic polymorphisms of these genes that may be causal to less severe behavioral conditions or to variations in behavior within a range considered normal. •
Project Title: NEUROPHYSIOLOGICAL CHARACTERIZATION OF WILLIAMS SYNDROME Principal Investigator & Institution: Mills, Debra L.; Associate Professor; Salk Institute for Biological Studies 10010 N Torrey Pines Rd La Jolla, Ca 920371099 Timing: Fiscal Year 2005 Summary: The goal of this research is to characterize the electrophysiological phenotypes of sensory and cognitive processing in individuals with Williams Syndrome (WS) and to link variability in the expression of these phenotypes to variability in brain structure, neurocognitive and genetic profiles as determined in projects I-5, respectively. To this end, event-related potentials (ERPs) will be recorded from 32 channels to examine the timing and topography of brain activity linked to 1) differential activation of the dorsal and ventral visual streams, 2) the effects of emotion on processing facial expressions and verbal declarative memory systems, and 3) the organization of semantic and syntactic processing in auditory sentences. These studies are linked with and depend upon the findings from projects I and III. Behavioral (accuracy and reaction times) and ERP data from these experiments will be compared with behavioral measures from similar paradigms and standardized tests described in Project V. Variability in ERP amplitudes will also be compared with that individual's measurement of brain structure for the specific areas of the brain known to mediate that function (in conjunction with Project III), e.g. variability in the latency amplitude and
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distribution of ERPs linked to differential activation of the dorsal versus ventral visual streams will be compared with measurements of brain regions known to mediate dorsal versus ventral visual processing. The topography of ERPs linked to visual and emotional processing will be compared with the topography of brain activity in the fMRI studies using the same paradigms. Links between abnormal brain function and genetic profiles (Project I) will be conducted by characterizing patterns of activity typical of individuals with WS with a full deletion and comparing these patterns with ERPs from individuals with different genetic profiles such as atypical deletions or parent of origin of the deletion for WS. More generally, these findings in turn will be elucidated by information regarding histochemical and cytoarchitectonic abnormalities in the WS brain (Project IV). •
Project Title: NUMERICAL DEFICITS ACROSS MULTIPLE GENETIC DISORDERS Principal Investigator & Institution: Simon, Tony J.; Research Assistant; Psychiatry & Behavioral Sciences; University of California Davis Office of Research - Sponsored Programs Davis, Ca 95618 Timing: Fiscal Year 2005; Project Start 01-FEB-2005; Project End 31-JUL-2008 Summary: (provided by applicant): The central aim of the proposed research is to investigate whether there is a common basis for the numerical cognition deficits associated with three neurogenetic disorders: Turner, Williams, and full mutation fragile X syndromes. Despite many differences, numerical deficits have been consistently reported in individuals with Turner, Williams, full mutation fragile X, and 22q11.2 deletion (velocardiofacial/DiGeorge) syndromes, among others. The investigators hypothesize that some key aspects of visuospatial function are disturbed in each of these syndromes, and characterization of these basic processes will generate explanations of, and possibly indicate treatments for, these numerical deficits. On the other hand, the differences among these genetic syndromes will allow the investigators to control for a range of critical factors such as intelligence level, brain volume, cardiac status, and other cognitive performance domains. This project aims to study seven to fourteen year old children with Williams, Turner, and full mutation fragile X syndromes in parallel with a study of 22q11.2 deletion syndrome children already being carried out by the principal investigator. This will constitute the first parallel study of children with all of these disorders using the same methodology. Thus it has the potential to reveal critical information about a putative "common pathway" for foundational numerical cognitive competence. Little is known about why a set of neurogenetic disorders that produce such different physical and intellectual outcomes should share what appears to be a common deficit in the numerical cognition domain. The investigators' hypothesis is that the disorders all create some form of anomalous in brain development that affects the parietal lobes, as well as other brain areas, in such a way as to disturb the normal development of visual/spatial cognition. Therefore, the investigators propose a program of research in three genetic disorders: Turner, Williams, full mutation fragile X syndromes with the following aims: (1) Characterize the cognitive deficit with performance tests; (2) Specify the volumetric changes in brains of children with these disorders; (3) Determine, via diffusion tensor imaging, white matter anomalies that might contribute to cognitive dysfunction; and (4) Directly measure, via functional magnetic resonance imaging (fMRI), cortical activity as children attempt visuospatial and numerical cognition tasks. The investigators expect that the results of these studies will provide the first extensive explanation of the similarities and/or differences in foundational numerical cognitive processes that exist among these different disorders. Findings are likely to indicate critical neurocognitive factors in the development of normal and disturbed early numerical ability. It should be possible to use these results
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to develop interventions for children with numerical disabilities and improved teaching methods in the numerical domain for typically developing children. •
Project Title: OBJECT AND SPACE PROCESSING: A DEVELOPMENTAL PERSPECTIVE Principal Investigator & Institution: Paul, Brianna M.; Center for Human Development; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2005; Project Start 01-JUL-2003; Project End 30-JUN-2006 Summary: (provided by applicant): Fundamental human abilities such as recognizing a loved one, or navigating with a map depend integrally on the extra striate visual cortex. Interestingly, the developmental course of this system is a protracted one, with certain skills continuing to develop into the teenage years. In the adult, higher order visual functions can be divided according to the neuroanatomical subsystems ("what" or ventral occipitotemporal, and "where" or dorsal occipitoparietal) on which they rely. Though a great deal is known regarding these systems in the adult, little is known about the development of these pathways and the emergence of this adult-like dissociation. The proposed studies, therefore, aim to address these uncertainties by utilizing a matched-task paradigm. The "what" task involves perceptual object-matching and the "where" task involves perceptual location-matching; these tasks are matched in that they are identical with respect to stimuli, required response and level of difficulty in adult controls. Study 1 will compare patterns of reaction time performance on these tasks for typical adults and children, with the goal being to explicate developmental changes and examine the emergence of the adult-like behavioral dissociation in what/where processing. Study 2 utilizes functional magnetic resonance imaging (fMRI) to characterize and compare developmental change in the neural substrates underlying "what" and "where" visual processing. Knowledge regarding the relationship between behavioral changes in these systems manifested during development and functional brain activity will allow for the systematic examination of alternative developmental trajectories of these higher order visual functions. Specifically, Study 3 will examine behavioral performance indices and functional brain activity in individuals with congenital/genetic abnormalities (Williams Syndrome) and in individuals who have experienced a prenatal stroke. These populations, thus, afford us the unique opportunity to begin to understand the nature of plasticity and reorganization in these critical perceptual systems.
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Project Title: PERIODIC LIMB MOVEMENTS IN WILLIAMS SYNDROME Principal Investigator & Institution: Mason, Thornton B.; Children's Hospital of Philadelphia Joseph Stokes, Jr. Research Institute Philadelphia, Pa 191044318 Timing: Fiscal Year 2005; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Candidate's Plans/Training: The candidate plans a career as a patient-oriented researcher bridging pediatric medicine, sleep disorders, and genetics. Training will include formal epidemiology and biostatistics course work, structured laboratory work, and closely mentored completion of the research protocol. Environment: The outstanding pediatric research setting at UPCHP includes expertise in sleep disorders, clinical genetics, and molecular biology. These areas of strength will be complemented by the clinical and basic science research support offered by the Center for Sleep and Respiratory Neurobiology. Pennsylvania's Center for Clinical Epidemiology and Biostatistics will provide formal course training. Collectively, the environment is uniquely suited for this training award. Research: PLMS are rhythmic and highly stereotyped flexion movements of the extremities. PLMS may produce
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significant sleep disruption, and occur over a range of patient ages and settings. The pathophysiology of PLMS is unknown. Although family studies suggest a genetic basis for some cases of PLMS occurring with restless legs syndrome, no associated genes or gene products have been identified. Because preliminary data support the paucity of PLMS among control subjects and the prominence of PLMS in children with WS, this special group of patients may represent a unique opportunity to allow identification of a gene(s) involved in PLMS. WS is a human developmental disorder caused by a microdeletion of multiple genes in a distinct region of chromosome 7 (7q11.23). In this protocol, I propose to test the specific hypothesis that children with WS manifest genetically determined PLMS that is responsive to dopaminergic therapy. To this end, the primary aims of this proposal are: 1) to determine the prevalence of PLMS and the degree of variability in children with WS; 2) to determine whether PLMS are sensitive to dopamine therapy as are PLMS to other populations; and 3) to determine if there is a specific PLMS-genotype correlation in patients with WS. This protocol will provide new insights into WS as a model for PLMS in the general population, and may identify a specific gene(s) implicated in the etiology of these movements. Further, it will provide training necessary to conduct rigorous patient-oriented research in the area of genetics of sleep and its disorders. •
Project Title: PSYCHOPATHOLOGY IN YOUNG PEOPLE WITH MENTAL RETARDATION Principal Investigator & Institution: Hofer, Scott M.; Professor; Gerontology Center; Pennsylvania State University-Univ Park 110 Technology Center Building University Park, Pa 16802 Timing: Fiscal Year 2005; Project Start 01-APR-2000; Project End 31-JAN-2008 Summary: (provided by applicant): The purpose of this application is to support an ongoing program of research aimed at determining risk and resilience factors in the evolution of psychopathology in an internationally unique cohort of young people with mental retardation that forms the Australian Child to Adult Development (ACAD) Study. The broad aims of this application are to 1) study the course and pattern of psychopathology in children with mental retardation; 2) examine potential biopsychosocial risk and protective factors which may be associated with psychopathology; and 3) evaluate and refine the measurement properties of the DEC, the principal instrument used to assess psychopathology in this study and in broad use internationally. The fourth wave of the ACAD study (14 years of follow-up) has now been completed and permits analysis of the development of psychopathology from childhood through adolescence to young adulthood. Advanced statistical methods, including growth mixture models, will be used to identify developmental trajectories of emotional and behavioral disturbance in these groups, to investigate risk, mediating and moderating factors, and to empirically delineate subpopulations showing distinct patterns of change over time. A separate aim is to evaluate and refine the psychometric properties of the Developmental Behavioral Checklist (DEC) in the longitudinal ACAD study and in several international cross-sectional datasets. The analysis of psychometric properties of the DEC will use new developments for multiple-group factor analysis of categorical data and item-response models to construct and evaluate a short-form measure of psychopathology. This application provides an extraordinary opportunity to evaluate the mental health pathway of this vulnerable population through the transition into adulthood. The unifying purpose of this project is to apply advanced statistical modeling techniques to the existing ACAD data and to strengthen the findings by incorporating comparable data collected in a number of other countries.
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Project Title: SOCIAL COGNITION IN WILLIAMS SYNDROME Principal Investigator & Institution: Tager-Flusberg, Helen B.; Professor; Anatomy and Neurobiology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 021182394 Timing: Fiscal Year 2006; Project Start 29-SEP-1995; Project End 31-MAR-2011 Summary: (provided by applicant): The main goals of our research program are to advance our understanding of the social phenotype of Williams syndrome (WS), and to define the cognitive mechanisms that underlie the unique social-affective features that define this neurodevelopmental disorder. Our current studies have demonstrated that adolescents and adults with WS are better than age and IQ matched learning disabled/mentally retarded controls oh standardized measures of face recognition, and in their ability to interpret prosodic cues to speakers' emotions in filtered speech, performing at similar levels to normal controls on these tasks. Moreover, they are more likely to notice subtle changes to social aspects of complex scenes, respond more empathically toward a person in distress, and on psychophysiological measures of arousal, appear to find social-affective stimuli less threatening than other people. In the next award period we plan to continue this line of research addressing the following questions: (1) Do people with WS show the same developmental changes during the early adolescent stage in face recognition as do controls? (2) Do people with WS interpret eye gaze information in the same way as controls? (3) Do people with WS show greater sensitivity to affective information in faces compared to controls using implicit tasks? (4) Do people with WS attend more than controls to social information in dynamic scenes, as evidenced by eye-tracking data? (5) Do people with WS find social stimuli differentially more rewarding than controls? (6) Do people with WS find socialaffective stimuli less threatening, as evidenced by psychophysiological measures of arousal, than controls? We plan to investigate these questions in a series of experiments comparing adolescents and young adults with WS to age/IQ matched and normal agematched controls, and predict that experiments addressing questions (1) - (2) will find comparable patterns of performance in the WS and control participants. In contrast, experiment addressing questions (3) - (6) will highlight unique performance patterns in WS, reflecting their greater attention and singular affective response to social information. This research program will not only advance our understanding of WS; it has the potential to influence developing theoretical models in the growing field of social cognitive neuroscience.
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Project Title: SOCIAL-EMOTIONAL FUNCTIONING-CHILDREN WILLIAMS SYNDROME Principal Investigator & Institution: Plesa Skwerer, Daniela; Anatomy and Neurobiology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 021182394 Timing: Fiscal Year 2006; Project Start 05-MAR-2006; Project End 29-FEB-2008 Summary: (provided by applicant): Williams syndrome (WS) is a genetically based disorder associated with a distinctive social and behavioral phenotype, characterized by a mixture of unique aspects of sociability (e.g., keen social attention, overfriendliness toward strangers, empathy), and impairments commonly found in other populations with mental retardation (e.g., in theory of mind, social perception and cognition, in socio-communicative behavior). Although recent studies have focused on defining the social-perceptual and social-cognitive abilities of people with WS, a comprehensive characterization of their social-behavioral profile and its developmental trajectory has not yet been achieved. The goal of the proposed research is to investigate the
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developmental roots of the apparently contrasting aspects of the social-behavioral phenotype of WS. In this pilot investigation we plan to focus on how three essential components involved in early socio-affective functioning - attachment relations, temperament, and style of interactive behavior - relate to distinct patterns of social behavior in WS, specifically, to empathic responsiveness. We hypothesize that the roots of the unique empathy documented in people with WS lie in their atypical approachbehavior toward strangers, coupled with a disinhibited personality. Children with WS aged between 30 and 42 months will be compared to age- and developmental levelmatched children with Down syndrome and to typically developing children matched on age, in a series of assessments of attachment relations, temperament, style of dyadic interaction, and empathic responsiveness in different contexts. These assessments will involve a combination of laboratory observations based on semi-structured activities with familiar and unfamiliar social partners (adults and peers), and questionnaires and interviews with children's primary caregivers. To capture developmental relations between these domains, assessments of attachment, temperament, socio-interactive behavior and cognitive-linguistic abilities in Year 1 will be followed one year later with assessments of socioemotional competence and empathy. We predict that children with WS will show distinctive behavioral patterns in these domains of social functioning, but that some of these differences will be mediated by the social context in which the behaviors occur and the time of assessment. The results of this investigation will provide preliminary data for a model of the developmental trajectory of social-affective functioning in WS, which might begin to explain the unique patterns of social behavior and social understanding in this distinctive syndrome, and may have implications for designing intervention strategies to enhance social skills in children with developmental disorders. •
Project Title: SPATIAL REPRESENTATION IN WILLIAMS SYNDROME Principal Investigator & Institution: Landau, Barbara; Professor; Psychology; Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680 Timing: Fiscal Year 2005; Project Start 05-JUL-2005; Project End 30-APR-2010 Summary: (provided by applicant): The central goal of this research is to understand the nature of spatial representations, its structure, normal development, and breakdown under conditions of genetic deficit. This goal will be accomplished by studying spatial representations in children and adults with Williams syndrome (WS)~ a rare genetic defect which gives rise to an unusual cognitive profile of severe spatial deficit coupled with relatively spared language. People with WS typically show severe deficits in visual construction tasks. Yet they show spared capacities to recognize objects, process visual motion, and talk about space. This unusual pattern of deficit and sparing suggests the broad hypothesis that dorsal stream functions of the brainmany of them parietal functions- are damaged in Williams syndrome. The pattern also suggests that ventral stream functions, such as object recognition may be spared, and that the combination of damage and sparing leads to the unusual spatial profile of WS. We will test the hypotheses that the WS spatial profile (a) reflects breakdown in multiple dorsal-parietal functions, including visual-spatial attention, updating for action, and imaginal transformations, (b) reflects sparing of object representation, a key ventral stream function, and (c) reflects severe delay or arrest at an early point along the normal developmental trajectory. Experimental probes will test these hypotheses in 4 projects examining visual attention, object representation, visual-manual action, and navigation. This research will shed light on theories of the normal architecture of spatial representation, how it develops in children, and its breakdown during development. The latter holds promise for understanding how to enhance normal spatial
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representations and build upon deficient ones. The research will have broad impact by increasing our understanding of how spatial systems develop in normal and impaired children. This understanding can afford insights to the applied community which depends on such research to develop interventions. •
Project Title: STUDIES OF PROSODY.AUTISTIC SPECTRUM DISORDERS Principal Investigator & Institution: Paul, Rhea; Professor; Communication Disorders; Southern Connecticut State University 501 Crescent St New Haven, Ct 065151330 Timing: Fiscal Year 2005; Project Start 23-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): The proposed project will provide 50% salary support for five years to release the applicant from teaching and other faculty responsibilities at Southern Connecticut State University and allow her to work on a series of patient-oriented research studies and to mentor beginning speech-language clinicians at the Yale Child Study Center. The candidate is a productive researcher (60 papers in refereed journals) who has, for the past 16 years, been teaching at state universities with heavy teaching loads. This award would provide her with the opportunity to engage in focused research and mentoring activities in a patient-oriented clinical research environment. The Yale Child Study Center has been active in both research and clinical care of children with autism for more than 20 years. The Center provides both a source of subjects for research and a multidisciplinary clinic that serves large numbers of these children and their families, as well as the opportunities for collaborations with scientists from a broad range of backgrounds. The candidate's longterm goals in this project are: 1) to increase her knowledge and skills in three areas in which specific collaborators have been proposed--instrumental speech analysis and signal detection, neuroimaging, and robotics; and 2) to devote more time and attention to patient-oriented research and clinical mentoring. The research career development plan proposed here will result in maximizing the candidate's opportunity to contribute to knowledge and practice in the field of communication disorders in autism. The research plan for this project involves three studies: 1) the study of the production of prosody in grammatical and pragmatic/affective contexts in high functioning individuals with autistic spectrum disorders (ASDs) and appropriate contrast groups, using instrumental analysis and signal detection methodologies, both to better detail prosodic abilities and to work toward the development of a prosodic intervention protocol; 2) the study of the perception of prosody in grammatical and pragmatic/affective contexts in high functioning individuals with ASDs and appropriate contrast groups, both to better detail their abilities and to work toward the development of a protocol that can be tested via functional magnetic resonance imaging for future studies of the neural organization of prosody and to investigate differences in processing strategies between typical subjects and those with ASDS; and 3) the development of a prosodic intervention program with a robotic generalization training phase, to be tested against a traditional intervention program.
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Project Title: THE ROLE OF EXPERIENCE IN THE DEVELOPMENT OF SPATIAL WORKING MEMORY Principal Investigator & Institution: Schutte, Anne R.; Psychology; University of Nebraska Lincoln Lincoln, Ne 685880430 Timing: Fiscal Year 2006; Project Start 01-AUG-2006; Project End 31-MAY-2008 Summary: (provided by applicant): Spatial working memory deficits occur in many developmental disabilities, including ADHD, Williams Syndrome, and autism. Despite the ubiquitous nature of spatial working memory deficits, very little is known about the
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normative development of spatial working memory. One thing researchers have identified, is a transition in spatial working memory early in development; however, researchers examining this transition have focused on what is changing, and have not explained what causes this change in spatial working memory. Before interventions can be developed for children with spatial memory deficits, it is necessary to determine what affects the development of spatial working memory. The goal of the research proposed here is to begin to examine how experience modulates spatial working memory development using a neural network model, the dynamic field theory, as a guide. The proposed research will use microgenetic methods to begin to examine the role of different types of experience in stimulating the development of spatial working memory. Specifically, children near the transition point will be given additional experience to determine if experience can "push" them through the transition earlier than children not receiving additional experience. Thus, the first aim of this research is to determine whether children given task-specific experience in a SWM task will transition earlier than a control group not receiving this experience. The second aim is to determine whether children given experience discriminating locations around the midline reference axis will transition earlier in the SWM task than a control group that does not receive any relevant experience. Experience that makes the reference axis more salient should cause children to transition. The third aim is to examine whether experience in one task generalizes to a second task. If the changes that result from additional experience are task general, they should generalize to a different SWM task. Determining how different types of experience affect the development of spatial working memory will provide us with a better understanding of the processes underlying spatial working memory. Understanding these processes will lead to a better understanding of spatial working memory deficits, and the development of interventions to alleviate these deficits. •
Project Title: CHROMATIN
TRANSCRIPTIONAL
ACTIVATION
BY
REORGANIZING
Principal Investigator & Institution: Bartholomew, Blaine; Associate Professor; Medical Biochemistry; Southern Illinois University Carbondale 900 S. Normal, Woody Hall C206 Carbondale, Il 629014709 Timing: Fiscal Year 2005; Project Start 01-JAN-1993; Project End 31-DEC-2005 Summary: (provided by applicant): Chromatin remodeling serves as a functional key in multiple cellular processes, one of them being the regulation of gene expression through promoting formation of the transcription complex and elongation of the transcription complex. There are several well-documented examples of chromatin remodeling complexes working in conjunction with gene-specific transcription factors to make the DNA accessible to the transcription machinery. In addition, the nucleosome structure is a severe deterrent to the rearrangement of genes required for the production of immunoglobulins. Chromatin remodeling is apparently a mechanism used to tightly regulate vertebrate immune systems and is probably the key to the molecular mechanism underlying the "accessibility hypothesis" proposed 15 years ago. Chromatin remodeling is also involved in cell cycle control and interacts with the tumor suppressor protein Rb or retinoblastoma protein. In understanding how SWI/SNF and ISW2 remodel the nucleosome, it is important to know that it does not work randomly on chromatin, but they are recruited or targeted to specific locations by gene-specific transcription factors or repressors. Evidence indicates that chromatin remodeling can be tightly coordinated with DNA modifications such as methylation of DNA and DNA replication. The list of diseases linked to chromatin remodeling continues to grow and includes such diseases as rhabdoid tumours, a very aggressive form of pediatric cancers,
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breast cancer, leukemia, mental retardation, Williams syndrome, and Rett syndrome. It is not known which subunits of SWI/SNF interact with the transcription activator or how its interaction with the nucleosome may be different when recruited versus indiscriminate binding to nucleosomes. Our research plan is to examine the structure and its relation to function of the SWI/SNF chromatin remodeling complex by a series of approaches that uses either modified DNA or modified histone octamers. We will obtain the 3-dimensional structure of SWI/SNF by electron tomography and determine which regions interact with DNA and histone octamer by linking data from site-directed photoaffinity labeling and proteolysis to the structure. Next, we will determine how SWI/SNF and ISW2 remodel chromatin when recruited to specific sites within nucleosomal arrays by their respective "targeting" proteins. Data on these two different chromatin remodeling complexes suggest that they modulate chromatin structure in significantly different ways both in vivo and in vitro. •
Project Title: VISUAL DETECTION AND INTEGRATION IN WILLIAMS SYNDROME Principal Investigator & Institution: Palomares, Melanie C.; Ophthalmology; Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680 Timing: Fiscal Year 2005; Project Start 16-JUN-2004; Project End 15-JUN-2006 Summary: (provided by applicant): I propose to characterize the basic visual abilities of children and adults with Williams Syndrome (WS), and of normally developing children. Williams Syndrome is a rare genetic disorder that has a distinct cognitive profile: a relative strength in language, but a profound weakness in visual-spatial cognition. This profile is of great interest because it suggests the possibility that genetic deficit might target specific cognitive systems, in this case, the system of spatial cognition. To date, most studies with WS have used complex visuo-motor tasks such as drawing or block construction to evaluate their visual-spatial abilities. Some have suggested that these deficits are not linked to "low-lever' visual functions such as stereopsis and acuity. However, very little is known about the abilities of WS in basic visual tasks. I plan to evaluate the possibility that the spatial cognitive deficits of WS are linked to important visual functions that allow integration of features over space. Using psychophysical tasks, I plan to look at how WS and normal controls detect a single object (e.g. detecting a grating at various spatial frequencies) as well as how they integrate multiple objects (e.g. detecting a contour made up of many gratings). These studies will give us a better understanding of how simple visual functions may contribute to complex spatial cognition deficits in WS, and perhaps provide insight into possible therapies that could ameliorate WS deficits. Furthermore, they will uncover the developmental trajectory of feature detection and feature integration in normal children.
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Project Title: VISUAL OBJECT REPRESENTATION IN WILLIAMS SYNDROME Principal Investigator & Institution: O'hearn, Kirsten M.; Cognitive Science; Johns Hopkins University W400 Wyman Park Building Baltimore, Md 212182680 Timing: Fiscal Year 2005; Project Start 17-JAN-2003; Project End 16-JAN-2006 Summary: This abstract is not available.
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Project Title: VISUAL-SOCIAL COGNITION IN NEURODEVELOPMENTAL DISORDERS Principal Investigator & Institution: Hadjikhani, Nouchine; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114
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Timing: Fiscal Year 2004; Project Start 30-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Visual perception of faces is a major component of the "online" processing of social information required for successful interaction with other individuals. Research from cognitive, clinical, and neuroscience approaches suggests that elements of the visual system may be specialized for processing human faces. Of particular interest is the dissociation of face processing from other categories of object processing, and from other components of visual processing, such as motion, attention, and spatial perception. Neuroimaging techniques have the potential to reveal aspects of the underlying architecture and function of visual processing. By combining data from functional magnetic resonance imaging (fMRI), magneto- and electroencephalography (MEG/EEG), and diffusion tensor imaging (DTI), we will be able to better understand the pathophysiology of three neurodevelopmental disorders: autism, Williams syndrome and developmental prosopagnosia. We will explore the dissociations observed in these three groups in order to better understand the fundamental architecture of the parts of the visual system involved with social cognition. Autistic disorder (ASD) and Williams syndrome (WS) seemingly offer complementary patterns of impaired and spared visual function. ASD individuals are poor at social interactions, at facial expression recognition but can perform well on spatial tasks, such as block design. WS individuals are hyper social, perform at ageappropriate levels on the Benton face recognition task, but are severely impaired at block construction and other spatial tasks. Another group of patients, developmental prosopagnosics (DP), are severely impaired in face recognition but are otherwise normal in all other cognitive and social domains. Our research goal will be to characterize the neural system underlying the visual-spatial and communicative aspects of face and object recognition in these three subject populations. We will examine the behavioral profile of ASD, WS and DP, and characterize their cognitive phenotypes in the domain of face processing. We will also analyze the visual cortex organization, at low (retinotopy), and intermediate (hierarchical attention) levels using fMRI, and at high levels (facial and emotional processing), in spatial and temporal domains using MEG and fMRI. Finally, we will examine the architecture of the visual stream subserving facial perception (including the amygdala) using Diffusion Tensor Imaging, Diffusion Spectrum Imaging, and cortical thickness analysis. These aims taken together should provide insight into the relation between behavioral performance and structural/functional characteristics. It should give us additional insight into the pathophysiology face perception disorders, and provide a basis for the development of remedial treatment for deficits in social communication. •
Project Title: WILLIAMS SYNDROME: BRIDGING COGNITION, BRAIN AND GENES Principal Investigator & Institution: Bellugi, Ursula; Research Professor; Salk Institute for Biological Studies 10010 N Torrey Pines Rd La Jolla, Ca 920371099 Timing: Fiscal Year 2005; Project Start 01-MAR-1997; Project End 28-FEB-2009 Summary: (provided by applicant): The overarching goal of this program project is to build bridges across disciplines, linking higher cognitive functions to their underlying neurobiological bases and their molecular genetic underpinnings using a specific genetic disorder, Williams syndrome (WS). To accomplish this goal, the program combines cognitive, electrophysiological, structural and functional imaging, histological, with molecular genetic approaches to study groups of individuals with WS. The findings of peaks and valleys of abilities in WS, including mild to moderate mental retardation in the context of a specific deficit in visuospatial processing, relative strengths in face
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processing and certain aspects of language, in addition to hypersociability. This unique profile makes WS an invaluable paradigm for the study of brain and behavior relationships, and for mapping to the genome. Program project: Project II, Neurophysiological Imaging characterizes the electrophysiological signature of the WS brain during sensory and cognitive processing. Project III: Functional Neuroimaging, uses multifaceted imaging techniques (high field-structural, functional, and diffusion tensor imaging) to identify neural pathways involved in WS cognition. Project IV. Molecular and Cellular Architectonics, explores histological and gene expression differences within brain areas associated with the cognitive profile of WS. Project I: Neurocognitive Characterization, will examine cognitive processing mechanisms and map sources of cognitive variability to neural pathways and variations in genetic expression. Studies from each project work interactively using integrated approaches to test hypotheses related to dorsoventral and posterior/anterior gradients in brain development, as well as changes within limbic system pathways as they relate to cognition and behavior. Together, these studies provide new opportunities for illuminating pathways among specific genes, neural systems, and cognitive functions.
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.12 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with Williams syndrome, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type Williams syndrome (or synonyms) into the search box, and click Go. The following is the type of output you can expect from PubMed for Williams syndrome (hyperlinks lead to article summaries): •
A case of Williams syndrome with a large, visible cytogenetic deletion. Author(s): Wu YQ, Nickerson E, Shaffer LG, Keppler-Noreuil K, Muilenburg A. Source: Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10636739&query_hl=23&itool=pubmed_docsum
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A componential view of theory of mind: evidence from Williams syndrome. Author(s): Tager-Flusberg H, Sullivan K. Source: Cognition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10822043&query_hl=23&itool=pubmed_docsum
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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A family of chromatin remodeling factors related to Williams syndrome transcription factor. Author(s): Bochar DA, Savard J, Wang W, Lafleur DW, Moore P, Cote J, Shiekhattar R. Source: Proceedings of the National Academy of Sciences of the United States of America. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10655480&query_hl=23&itool=pubmed_docsum
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A longitudinal assessment of diverging verbal and non-verbal abilities in the Williams syndrome phenotype. Author(s): Jarrold C, Baddeley AD, Hewes AK, Phillips C. Source: Cortex. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11485066&query_hl=23&itool=pubmed_docsum
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A longitudinal study of language development in two children with Williams syndrome. Author(s): Levy Y. Source: Journal of Child Language. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15495842&query_hl=23&itool=pubmed_docsum
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Abnormal cortical complexity and thickness profiles mapped in Williams syndrome. Author(s): Thompson PM, Lee AD, Dutton RA, Geaga JA, Hayashi KM, Eckert MA, Bellugi U, Galaburda AM, Korenberg JR, Mills DL, Toga AW, Reiss AL. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15843618&query_hl=23&itool=pubmed_docsum
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Adaptive behavior of 4- through 8-year-old children with Williams syndrome. Author(s): Mervis CB, Klein-Tasman BP, Mastin ME. Source: Am J Ment Retard. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11246716&query_hl=23&itool=pubmed_docsum
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Age-associated memory changes in adults with Williams syndrome. Author(s): Devenny DA, Krinsky-McHale SJ, Kittler PM, Flory M, Jenkins E, Brown WT. Source: Developmental Neuropsychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15525565&query_hl=23&itool=pubmed_docsum
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American Academy of Pediatrics: Health care supervision for children with Williams syndrome. Author(s): Committee on Genetics. Source: Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11331709&query_hl=23&itool=pubmed_docsum
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An experiment of nature: brain anatomy parallels cognition and behavior in Williams syndrome. Author(s): Reiss AL, Eckert MA, Rose FE, Karchemskiy A, Kesler S, Chang M, Reynolds MF, Kwon H, Galaburda A. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15163693&query_hl=23&itool=pubmed_docsum
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An investigation of verbal short-term memory and phonological processing in four children with Williams syndrome. Author(s): Majerus S, Barisnikov K, Vuillemin I, Poncelet M, van der Linden M. Source: Neurocase : Case Studies in Neuropsychology, Neuropsychiatry, and Behavioural Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14972754&query_hl=23&itool=pubmed_docsum
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Anaesthesia for MRI angiography in a patient with Williams syndrome. Author(s): Andrzejowski J, Mundy J. Source: Anaesthesia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10594455&query_hl=23&itool=pubmed_docsum
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Analysis of cerebral shape in Williams syndrome. Author(s): Schmitt JE, Eliez S, Bellugi U, Reiss AL. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11176967&query_hl=23&itool=pubmed_docsum
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Anomalous brain activation during face and gaze processing in Williams syndrome. Author(s): Mobbs D, Garrett AS, Menon V, Rose FE, Bellugi U, Reiss AL. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15184616&query_hl=23&itool=pubmed_docsum
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Anomalous sylvian fissure morphology in Williams syndrome. Author(s): Eckert MA, Galaburda AM, Karchemskiy A, Liang A, Thompson P, Dutton RA, Lee AD, Bellugi U, Korenberg JR, Mills D, Rose FE, Reiss AL. Source: Neuroimage. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16876437&query_hl=23&itool=pubmed_docsum
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Are numerical impairments syndrome specific? Evidence from Williams syndrome and Down's syndrome. Author(s): Paterson SJ, Girelli L, Butterworth B, Karmiloff-Smith A. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16423150&query_hl=23&itool=pubmed_docsum
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Assessment of the influence of background noise on escape-maintained problem behavior and pain behavior in a child with Williams syndrome. Author(s): O'Reilly MF, Lacey C, Lancioni GE. Source: J Appl Behav Anal. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11214027&query_hl=23&itool=pubmed_docsum
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Asynchrony in the cognitive and lexical development of young children with Williams syndrome. Author(s): Nazzi T, Gopnik A, Karmiloff-Smith A. Source: Journal of Child Language. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16045258&query_hl=23&itool=pubmed_docsum
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Autism and Williams syndrome: a case report. Author(s): Herguner S, Motavalli Mukaddes N. Source: World J Biol Psychiatry. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16861145&query_hl=23&itool=pubmed_docsum
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Aversion, awareness, and attraction: investigating claims of hyperacusis in the Williams syndrome phenotype. Author(s): Levitin DJ, Cole K, Lincoln A, Bellugi U. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15845131&query_hl=23&itool=pubmed_docsum
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Balloon dilation angioplasty of peripheral pulmonary stenosis associated with Williams syndrome. Author(s): Geggel RL, Gauvreau K, Lock JE. Source: Circulation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11331257&query_hl=23&itool=pubmed_docsum
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Behavioral and emotional disturbance in individuals with Williams syndrome. Author(s): Einfeld SL, Tonge BJ, Florio T. Source: Am J Ment Retard. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9241407&query_hl=23&itool=pubmed_docsum
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Behavioral features of CHARGE syndrome (Hall-Hittner syndrome) comparison with Down syndrome, Prader-Willi syndrome, and Williams syndrome. Author(s): Graham JM Jr, Rosner B, Dykens E, Visootsak J. Source: Am J Med Genet A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15637708&query_hl=23&itool=pubmed_docsum
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Bilateral vocal cord paralysis in Williams syndrome. Author(s): Stewart FJ, Dalzell M, McReid M, Cinnamond MJ. Source: Clinical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8275577&query_hl=23&itool=pubmed_docsum
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Biliary hypoplasia in Williams syndrome. Author(s): O'Reilly K, Ahmed SF, Murday V, McGrogan P. Source: Archives of Disease in Childhood. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16632669&query_hl=23&itool=pubmed_docsum
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Body composition, energy expenditure, and energy intake in patients with Williams syndrome. Author(s): Kaplan AS, Stallings VA, Zemel BS, Green KA, Kaplan P. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9506631&query_hl=23&itool=pubmed_docsum
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Brain biochemistry in Williams syndrome: evidence for a role of the cerebellum in cognition? Author(s): Chang L, Ernst T, Berman N. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10078767&query_hl=23&itool=pubmed_docsum
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Brain biochemistry in Williams syndrome: evidence for a role of the cerebellum in cognition? Author(s): Rae C, Karmiloff-Smith A, Lee MA, Dixon RM, Grant J, Blamire AM, Thompson CH, Styles P, Radda GK. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9674775&query_hl=23&itool=pubmed_docsum
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Bridging cognition, the brain and molecular genetics: evidence from Williams syndrome. Author(s): Bellugi U, Lichtenberger L, Mills D, Galaburda A, Korenberg JR. Source: Trends in Neurosciences. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10322491&query_hl=23&itool=pubmed_docsum
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Brief report: four case histories and a literature review of Williams syndrome and autistic behavior. Author(s): Gillberg C, Rasmussen P. Source: Journal of Autism and Developmental Disorders. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8050990&query_hl=23&itool=pubmed_docsum
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Brief report: response to methylphenidate in two children with Williams syndrome. Author(s): Power TJ, Blum NJ, Jones SM, Kaplan PE. Source: Journal of Autism and Developmental Disorders. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9018583&query_hl=23&itool=pubmed_docsum
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Burkitt lymphoma and Williams syndrome: a model for children with a multisystem disorder and malignancy. Author(s): Thornburg CD, Roulston D, Castle VP. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15701989&query_hl=23&itool=pubmed_docsum
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Can adolescents with Williams syndrome tell the difference between lies and jokes? Author(s): Sullivan K, Winner E, Tager-Flusberg H. Source: Developmental Neuropsychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12730021&query_hl=23&itool=pubmed_docsum
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Cardiac arrest under anesthesia in a pediatric patient with Williams syndrome: a case report. Author(s): Bragg K, Fedel GM, DiProsperis A. Source: Aana Journal. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16108410&query_hl=23&itool=pubmed_docsum
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Cardiovascular findings, and clinical course, in patients with Williams syndrome. Author(s): Bruno E, Rossi N, Thuer O, Cordoba R, Alday LE. Source: Cardiology in the Young. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14982294&query_hl=23&itool=pubmed_docsum
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Central precocious puberty in a girl with Williams syndrome: the result of treatment with GnRH analogue. Author(s): Utine GE, Alikasifoglu A, Alikasifoglu M, Tuncbilek E. Source: Eur J Med Genet. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16473313&query_hl=23&itool=pubmed_docsum
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Cerebellar abnormalities in infants and toddlers with Williams syndrome. Author(s): Jones W, Hesselink J, Courchesne E, Duncan T, Matsuda K, Bellugi U. Source: Developmental Medicine and Child Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12418794&query_hl=23&itool=pubmed_docsum
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Characterizing the musical phenotype in individuals with Williams Syndrome. Author(s): Levitin DJ, Cole K, Chiles M, Lai Z, Lincoln A, Bellugi U. Source: Child Neuropsychol. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15621847&query_hl=23&itool=pubmed_docsum
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Children with Prader-Willi syndrome vs. Williams syndrome: indirect effects on parents during a jigsaw puzzle task. Author(s): Ly TM, Hodapp RM. Source: Journal of Intellectual Disability Research : Jidr. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16287481&query_hl=23&itool=pubmed_docsum
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Clinical and molecular cytogenetic (FISH) diagnosis of Williams syndrome. Author(s): Brewer CM, Morrison N, Tolmie JL. Source: Archives of Disease in Childhood. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8660051&query_hl=23&itool=pubmed_docsum
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Clinical manifestations and molecular investigation of 50 patients with Williams syndrome in the Greek population. Author(s): Amenta S, Sofocleous C, Kolialexi A, Thomaidis L, Giouroukos S, Karavitakis E, Mavrou A, Kitsiou S, Kanavakis E, Fryssira H. Source: Pediatric Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15774842&query_hl=23&itool=pubmed_docsum
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Coeliac disease in Williams syndrome. Author(s): Giannotti A, Tiberio G, Castro M, Virgilii F, Colistro F, Ferretti F, Digilio MC, Gambarara M, Dallapiccola B. Source: Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11694549&query_hl=23&itool=pubmed_docsum
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Cognitive heterogeneity in Williams syndrome. Author(s): Porter MA, Coltheart M. Source: Developmental Neuropsychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15753050&query_hl=23&itool=pubmed_docsum
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Cognitive, lexical and morpho-syntactic profiles of Israeli children with Williams syndrome. Author(s): Levy Y, Bechar T. Source: Cortex. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12784888&query_hl=23&itool=pubmed_docsum
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Comparative genomic sequence analysis of the Williams syndrome region (LIMK1RFC2) of human chromosome 7q11.23. Author(s): Martindale DW, Wilson MD, Wang D, Burke RD, Chen X, Duronio V, Koop BF. Source: Mammalian Genome : Official Journal of the International Mammalian Genome Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11003705&query_hl=23&itool=pubmed_docsum
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Complete augmentation of diffuse narrowing of the aorta with Williams syndrome by using an overturn approach. Author(s): Yamagishi M, Shuntoh K, Matsushita T, Fujiwara K, Shinkawa T, Miyazaki T, Kitamura N. Source: The Journal of Thoracic and Cardiovascular Surgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12830088&query_hl=23&itool=pubmed_docsum
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Composite aortoplasty for recurrent coarctation after neonatal repair in Williams syndrome. Author(s): Marks JL, Mitchell MB, Campbell DN, Toews WH. Source: The Annals of Thoracic Surgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14726089&query_hl=23&itool=pubmed_docsum
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Comprehension of spatial language terms in Williams syndrome: evidence for an interaction between domains of strength and weakness. Author(s): Phillips CE, Jarrold C, Baddeley AD, Grant J, Karmiloff-Smith A. Source: Cortex. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15070004&query_hl=23&itool=pubmed_docsum
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Concomitant reentrant tachycardias from concealed accessory atrioventricular bypass tract and atrioventricular nodal reentry in a patient with Williams syndrome. Author(s): Kantharia BK, Mittleman RS. Source: Cardiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10545683&query_hl=23&itool=pubmed_docsum
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Configural and local processing of faces in children with Williams syndrome. Author(s): Deruelle C, Mancini J, Livet MO, Casse-Perrot C, de Schonen S. Source: Brain and Cognition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10585239&query_hl=23&itool=pubmed_docsum
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Coronary artery disease and anesthesia-related death in children with Williams syndrome. Author(s): Horowitz PE, Akhtar S, Wulff JA, Al Fadley F, Al Halees Z. Source: Journal of Cardiothoracic and Vascular Anesthesia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12486657&query_hl=23&itool=pubmed_docsum
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Corpus callosum morphology of Williams syndrome: relation to genetics and behavior. Author(s): Schmitt JE, Eliez S, Warsofsky IS, Bellugi U, Reiss AL. Source: Developmental Medicine and Child Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11263684&query_hl=23&itool=pubmed_docsum
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De novo 46,XX,t(6;7)(q27;q11;23) associated with severe cardiovascular manifestations characteristic of supravalvular aortic stenosis and Williams syndrome. Author(s): von Dadelszen P, Chitayat D, Winsor EJ, Cohen H, MacDonald C, Taylor G, Rose T, Hornberger LK. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10710222&query_hl=23&itool=pubmed_docsum
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Death following tonsillectomy in a child with Williams syndrome. Author(s): Monfared A, Messner A. Source: International Journal of Pediatric Otorhinolaryngology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16406078&query_hl=23&itool=pubmed_docsum
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Deletions at chromosome regions 7q11.23 and 7q36 in a patient with Williams syndrome. Author(s): Wouters CH, Meijers-Heijboer HJ, Eussen BJ, van der Heide AA, van Luijk RB, van Drunen E, Beverloo BB, Visscher F, Van Hemel JO. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11484204&query_hl=23&itool=pubmed_docsum
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Dental anomalies in Williams syndrome. Author(s): Kashyap AS, Sharma HS, Kumar P. Source: Postgraduate Medical Journal. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11060148&query_hl=23&itool=pubmed_docsum
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Dental characteristics in Williams syndrome: a clinical and radiographic evaluation. Author(s): Axelsson S, Bjornland T, Kjaer I, Heiberg A, Storhaug K. Source: Acta Odontologica Scandinavica. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12868685&query_hl=23&itool=pubmed_docsum
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Detection of an atypical 7q11.23 deletion in Williams syndrome patients which does not include the STX1A and FZD3 genes. Author(s): Botta A, Novelli G, Mari A, Novelli A, Sabani M, Korenberg J, Osborne LR, Digilio MC, Giannotti A, Dallapiccola B. Source: Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10874638&query_hl=23&itool=pubmed_docsum
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Dethroning the myth: cognitive dissociations and innate modularity in Williams syndrome. Author(s): Karmiloff-Smith A, Brown JH, Grice S, Paterson S. Source: Developmental Neuropsychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12730026&query_hl=23&itool=pubmed_docsum
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Differences by sex in cardiovascular disease in Williams syndrome. Author(s): Sadler LS, Pober BR, Grandinetti A, Scheiber D, Fekete G, Sharma AN, Urban Z. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11743512&query_hl=23&itool=pubmed_docsum
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Difficulty in writing Japanese semantic characters in a 9-year-old boy with Williams syndrome. Author(s): Nakamura M, Hara K, Watamaki T, Nishimura B, Kumagai T, Matsumoto A, Miura K, Yamanaka T, Hayakawa C, Miyazaki S. Source: Journal of Intellectual Disability Research : Jidr. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10622373&query_hl=23&itool=pubmed_docsum
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Disordered visual processing and oscillatory brain activity in autism and Williams syndrome. Author(s): Grice SJ, Spratling MW, Karmiloff-Smith A, Halit H, Csibra G, de Haan M, Johnson MH. Source: Neuroreport. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11522950&query_hl=23&itool=pubmed_docsum
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Disruption of the elastin gene in adult Williams syndrome is accompanied by a paradoxical reduction in arterial stiffness. Author(s): Lacolley P, Boutouyrie P, Glukhova M, Daniel Lamaziere JM, Plouin PF, Bruneval P, Vuong P, Corvol P, Laurent S. Source: Clinical Science (London, England : 1979). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12095400&query_hl=23&itool=pubmed_docsum
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Distinctive personality characteristics of 8-, 9-, and 10-year-olds with Williams syndrome. Author(s): Klein-Tasman BP, Mervis CB. Source: Developmental Neuropsychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12730028&query_hl=23&itool=pubmed_docsum
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Divergent human and mouse orthologs of a novel gene (WBSCR15/Wbscr15) reside within the genomic interval commonly deleted in Williams syndrome. Author(s): Doyle JL, DeSilva U, Miller W, Green ED. Source: Cytogenetics and Cell Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11124535&query_hl=23&itool=pubmed_docsum
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Divided attention, selective attention and drawing: processing preferences in Williams syndrome are dependent on the task administered. Author(s): Farran EK, Jarrold C, Gathercole SE. Source: Neuropsychologia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12591025&query_hl=23&itool=pubmed_docsum
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Do children with Williams syndrome fail to process visual configural information? Author(s): Deruelle C, Rondan C, Mancini J, Livet MO. Source: Research in Developmental Disabilities. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16005605&query_hl=23&itool=pubmed_docsum
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Dorsal forebrain anomaly in Williams syndrome. Author(s): Galaburda AM, Schmitt JE, Atlas SW, Eliez S, Bellugi U, Reiss AL. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11708996&query_hl=23&itool=pubmed_docsum
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Dorsal-stream motion processing deficits persist into adulthood in Williams syndrome. Author(s): Atkinson J, Braddick O, Rose FE, Searcy YM, Wattam-Bell J, Bellugi U. Source: Neuropsychologia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16168445&query_hl=23&itool=pubmed_docsum
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Drawing abilities in Williams syndrome: a case study. Author(s): Stiles J, Sabbadini L, Capirci O, Volterra V. Source: Developmental Neuropsychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11280965&query_hl=23&itool=pubmed_docsum
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Drawings by individuals with Williams syndrome: are people different from shapes? Author(s): Dykens EM, Rosner BA, Ly TM. Source: Am J Ment Retard. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11246717&query_hl=23&itool=pubmed_docsum
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Dysphagia: an unusual presentation of giant aneurysm of the right coronary artery and supravalvular aortic stenosis in Williams syndrome. Author(s): Mignosa C, Agati S, Di Stefano S, Pizzimenti G, Di Maggio E, Salvo D, Ciccarello G. Source: The Journal of Thoracic and Cardiovascular Surgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15573082&query_hl=23&itool=pubmed_docsum
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Early development (5 to 48 months) in Williams syndrome. A study of 14 children. Author(s): Plissart L, Fryns JP. Source: Genet Couns. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10422008&query_hl=23&itool=pubmed_docsum
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Early development of children with Williams syndrome. Author(s): Sarimski K. Source: Genet Couns. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10422007&query_hl=23&itool=pubmed_docsum
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Early linguistic abilities of Italian children with Williams syndrome. Author(s): Volterra V, Caselli MC, Capirci O, Tonucci F, Vicari S. Source: Developmental Neuropsychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12730019&query_hl=23&itool=pubmed_docsum
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Early puberty in Williams syndrome. Author(s): Cherniske EM, Sadler LS, Schwartz D, Carpenter TO, Pober BR. Source: Clinical Dysmorphology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10319200&query_hl=23&itool=pubmed_docsum
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Elastin gene deletions in Williams syndrome patients result in altered deposition of elastic fibers in skin and a subclinical dermal phenotype. Author(s): Urban Z, Peyrol S, Plauchu H, Zabot MT, Lebwohl M, Schilling K, Green M, Boyd CD, Csiszar K. Source: Pediatric Dermatology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10720981&query_hl=23&itool=pubmed_docsum
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Elastin gene deletions in Williams syndrome. Author(s): Smoot LB. Source: Current Opinion in Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8776022&query_hl=23&itool=pubmed_docsum
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Elastin mutation is associated with a reduced gain of the baroreceptor--heart rate reflex in patients with Williams syndrome. Author(s): Girard A, Sidi D, Aggoun Y, Laude D, Bonnet D, Elghozi JL. Source: Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12102453&query_hl=23&itool=pubmed_docsum
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Elastin region deletions in Williams syndrome. Author(s): Zhang J, Kumar A, Roux K, Williams CA, Wallace MR. Source: Genetic Testing. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10627943&query_hl=23&itool=pubmed_docsum
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Elevated ambulatory blood pressure in 20 subjects with Williams syndrome. Author(s): Broder K, Reinhardt E, Ahern J, Lifton R, Tamborlane W, Pober B. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10232742&query_hl=23&itool=pubmed_docsum
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Enlarged cerebellar vermis in Williams syndrome. Author(s): Schmitt JE, Eliez S, Warsofsky IS, Bellugi U, Reiss AL. Source: Journal of Psychiatric Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11578640&query_hl=23&itool=pubmed_docsum
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ERP abnormalities of illusory contour perception in Williams syndrome. Author(s): Grice SJ, Haan MD, Halit H, Johnson MH, Csibra G, Grant J, Karmiloff-Smith A. Source: Neuroreport. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14534418&query_hl=23&itool=pubmed_docsum
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Evaluation of arterial stiffness in children with Williams syndrome: Does it play a role in evolving hypertension? Author(s): Salaymeh KJ, Banerjee A. Source: American Heart Journal. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11526372&query_hl=23&itool=pubmed_docsum
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Evidence for superior parietal impairment in Williams syndrome. Author(s): Eckert MA, Hu D, Eliez S, Bellugi U, Galaburda A, Korenberg J, Mills D, Reiss AL. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15642924&query_hl=23&itool=pubmed_docsum
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Evidence for unusual spatial location coding in Williams syndrome: an explanation for the local bias in visuo-spatial construction tasks? Author(s): Farran EK, Jarrold C. Source: Brain and Cognition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16043277&query_hl=23&itool=pubmed_docsum
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Exercise testing and 24-hour ambulatory blood pressure monitoring in children with Williams syndrome. Author(s): Giordano U, Turchetta A, Giannotti A, Digilio MC, Virgilii F, Calzolari A. Source: Pediatric Cardiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11894156&query_hl=23&itool=pubmed_docsum
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Exploring the Williams syndrome face-processing debate: the importance of building developmental trajectories. Author(s): Karmiloff-Smith A, Thomas M, Annaz D, Humphreys K, Ewing S, Brace N, Duuren M, Pike G, Grice S, Campbell R. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15335346&query_hl=23&itool=pubmed_docsum
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Expression analysis and protein localization of the human HPC-1/syntaxin 1A, a gene deleted in Williams syndrome. Author(s): Botta A, Sangiuolo F, Calza L, Giardino L, Potenza S, Novelli G, Dallapiccola B. Source: Genomics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10644452&query_hl=23&itool=pubmed_docsum
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Expressive vocabulary ability of toddlers with Williams syndrome or Down syndrome: a comparison. Author(s): Mervis CB, Robinson BF. Source: Developmental Neuropsychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10916578&query_hl=23&itool=pubmed_docsum
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Extended aortic and left main coronary angioplasty with a single pericardial patch in a patient with Williams syndrome. Author(s): Matsuda H, Miyamoto Y, Takahashi T, Kadoba K, Nakano S, Sano T. Source: The Annals of Thoracic Surgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1755690&query_hl=23&itool=pubmed_docsum
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Face and place processing in Williams syndrome: evidence for a dorsal-ventral dissociation. Author(s): Paul BM, Stiles J, Passarotti A, Bavar N, Bellugi U. Source: Neuroreport. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12151752&query_hl=23&itool=pubmed_docsum
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Facial and dental appearance of Williams syndrome. Author(s): Tarjan I, Balaton G, Balaton P, Varbiro S, Vajo Z. Source: Postgraduate Medical Journal. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12743349&query_hl=23&itool=pubmed_docsum
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Facial expression recognition in Williams syndrome. Author(s): Gagliardi C, Frigerio E, Burt DM, Cazzaniga I, Perrett DI, Borgatti R. Source: Neuropsychologia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12591030&query_hl=23&itool=pubmed_docsum
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Familial occurrence of the Williams syndrome. Author(s): White RA, Preus M, Watters GV, Fraser FC. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=908984&query_hl=23&itool=pubmed_docsum
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Familial Williams syndrome. Author(s): Cortada X, Taysi K, Hartmann AF. Source: Clinical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7192194&query_hl=23&itool=pubmed_docsum
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Family contexts, parental behaviour, and personality profiles of children and adolescents with Prader-Willi, fragile-X, or Williams syndrome. Author(s): van Lieshout CF, De Meyer RE, Curfs LM, Fryns JP. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9690933&query_hl=23&itool=pubmed_docsum
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Fears, hyperacusis and musicality in Williams syndrome. Author(s): Blomberg S, Rosander M, Andersson G. Source: Research in Developmental Disabilities. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16269236&query_hl=23&itool=pubmed_docsum
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Figure copying in Williams syndrome and normal subjects. Author(s): Georgopoulos MA, Georgopoulos AP, Kurz N, Landau B. Source: Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14968282&query_hl=23&itool=pubmed_docsum
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FISH analysis in patients with clinical diagnosis of Williams syndrome. Author(s): Elcioglu N, Mackie-Ogilvie C, Daker M, Berry AC. Source: Acta Paediatrica (Oslo, Norway : 1992). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9510447&query_hl=23&itool=pubmed_docsum
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Foreshortened dorsal extension of the central sulcus in Williams syndrome. Author(s): Jackowski AP, Schultz RT. Source: Cortex. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15871594&query_hl=23&itool=pubmed_docsum
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Free recall in Williams syndrome: is there a dissociation between short- and longterm memory? Author(s): Brock J, Brown GD, Boucher J. Source: Cortex. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16771042&query_hl=23&itool=pubmed_docsum
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Functional, structural, and metabolic abnormalities of the hippocampal formation in Williams syndrome. Author(s): Meyer-Lindenberg A, Mervis CB, Sarpal D, Koch P, Steele S, Kohn P, Marenco S, Morris CA, Das S, Kippenhan S, Mattay VS, Weinberger DR, Berman KF. Source: The Journal of Clinical Investigation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15951840&query_hl=23&itool=pubmed_docsum
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Generalized arteriopathy in Williams syndrome: an intravascular ultrasound study. Author(s): Rein AJ, Preminger TJ, Perry SB, Lock JE, Sanders SP. Source: Journal of the American College of Cardiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8496544&query_hl=23&itool=pubmed_docsum
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Generation and comparative analysis of approximately 3.3 Mb of mouse genomic sequence orthologous to the region of human chromosome 7q11.23 implicated in Williams syndrome. Author(s): DeSilva U, Elnitski L, Idol JR, Doyle JL, Gan W, Thomas JW, Schwartz S, Dietrich NL, Beckstrom-Sternberg SM, McDowell JC, Blakesley RW, Bouffard GG, Thomas PJ, Touchman JW, Miller W, Green ED. Source: Genome Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11779826&query_hl=23&itool=pubmed_docsum
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Genetic approaches to cardiovascular disease. Supravalvular aortic stenosis, Williams syndrome, and long-QT syndrome. Author(s): Keating MT. Source: Circulation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7788908&query_hl=23&itool=pubmed_docsum
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Genetic contributions to human gyrification: sulcal morphometry in Williams syndrome. Author(s): Kippenhan JS, Olsen RK, Mervis CB, Morris CA, Kohn P, Meyer-Lindenberg A, Berman KF. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16120786&query_hl=23&itool=pubmed_docsum
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Genetically dissociated components of working memory: evidence from Down's and Williams syndrome. Author(s): Jarrold C, Baddeley AD, Hewes AK. Source: Neuropsychologia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10390025&query_hl=23&itool=pubmed_docsum
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Genetics of childhood disorders: XXVI. Williams syndrome and brain-behavior relationships. Author(s): Schultz RT, Grelotti DJ, Pober B. Source: Journal of the American Academy of Child and Adolescent Psychiatry. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11349707&query_hl=23&itool=pubmed_docsum
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Genetics of childhood disorders: XXVII. Genes and cognition in Williams syndrome. Author(s): Osborne L, Pober B. Source: Journal of the American Academy of Child and Adolescent Psychiatry. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11392353&query_hl=23&itool=pubmed_docsum
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Genomic organization of the genes Gtf2ird1, Gtf2i, and Ncf1 at the mouse chromosome 5 region syntenic to the human chromosome 7q11.23 Williams syndrome critical region. Author(s): Bayarsaihan D, Dunai J, Greally JM, Kawasaki K, Sumiyama K, Enkhmandakh B, Shimizu N, Ruddle FH. Source: Genomics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11827466&query_hl=23&itool=pubmed_docsum
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Genotype-phenotype correlation in two sets of monozygotic twins with Williams syndrome. Author(s): Castorina P, Selicorni A, Bedeschi F, Dalpra L, Larizza L. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9066894&query_hl=23&itool=pubmed_docsum
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Global and local processing in Williams syndrome, autism, and Down syndrome: perception, attention, and construction. Author(s): Porter MA, Coltheart M. Source: Developmental Neuropsychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17083292&query_hl=23&itool=pubmed_docsum
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Growth of the aorta in children with Williams syndrome: does surgery make a difference? Author(s): English RF, Colan SD, Kanani PM, Ettedgui JA. Source: Pediatric Cardiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14758447&query_hl=23&itool=pubmed_docsum
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GTF2I hemizygosity implicated in mental retardation in Williams syndrome: genotype-phenotype analysis of five families with deletions in the Williams syndrome region. Author(s): Morris CA, Mervis CB, Hobart HH, Gregg RG, Bertrand J, Ensing GJ, Sommer A, Moore CA, Hopkin RJ, Spallone PA, Keating MT, Osborne L, Kimberley KW, Stock AD. Source: Am J Med Genet A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14556246&query_hl=23&itool=pubmed_docsum
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Heat shock protein 27 gene: chromosomal and molecular location and relationship to Williams syndrome. Author(s): Stock AD, Spallone PA, Dennis TR, Netski D, Morris CA, Mervis CB, Hobart HH. Source: Am J Med Genet A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12838549&query_hl=23&itool=pubmed_docsum
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Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome. Author(s): Ewart AK, Morris CA, Atkinson D, Jin W, Sternes K, Spallone P, Stock AD, Leppert M, Keating MT. Source: Nature Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7693128&query_hl=23&itool=pubmed_docsum
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Hemizygous deletion of the HPC-1/syntaxin 1A gene (STX1A) in patients with Williams syndrome. Author(s): Nakayama T, Matsuoka R, Kimura M, Hirota H, Mikoshiba K, Shimizu Y, Shimizu N, Akagawa K. Source: Cytogenetics and Cell Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9763659&query_hl=23&itool=pubmed_docsum
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Hemizygous deletion of the syntaxin 1A gene in individuals with Williams syndrome. Author(s): Osborne LR, Soder S, Shi XM, Pober B, Costa T, Scherer SW, Tsui LC. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9311751&query_hl=23&itool=pubmed_docsum
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Hippocampal and visuospatial learning defects in mice with a deletion of frizzled 9, a gene in the Williams syndrome deletion interval. Author(s): Zhao C, Aviles C, Abel RA, Almli CR, McQuillen P, Pleasure SJ. Source: Development (Cambridge, England). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15930120&query_hl=23&itool=pubmed_docsum
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How common is precocious puberty in patients with Williams syndrome? Author(s): Scothorn DJ, Butler MG. Source: Clinical Dysmorphology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9018426&query_hl=23&itool=pubmed_docsum
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Human genetics: dissecting Williams syndrome. Author(s): Monaco AP. Source: Current Biology : Cb. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8939595&query_hl=23&itool=pubmed_docsum
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Hyperacusis and otitis media in individuals with Williams syndrome. Author(s): Klein AJ, Armstrong BL, Greer MK, Brown FR 3rd. Source: J Speech Hear Disord. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2329796&query_hl=23&itool=pubmed_docsum
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Hyperacusis and Williams syndrome. Author(s): Nigam A, Samuel PR. Source: The Journal of Laryngology and Otology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8027650&query_hl=23&itool=pubmed_docsum
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Hyperacusis in Williams syndrome. Author(s): Johnson LB, Comeau M, Clarke KD. Source: The Journal of Otolaryngology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11770962&query_hl=23&itool=pubmed_docsum
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Hyperacusis in Williams syndrome: a sample survey study. Author(s): Van Borsel J, Curfs LM, Fryns JP. Source: Genet Couns. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9219010&query_hl=23&itool=pubmed_docsum
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Hypercalcemic phase of Williams syndrome. Author(s): Bzduch V. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8355137&query_hl=23&itool=pubmed_docsum
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Hypothesis for development of a behavioral phenotype in Williams syndrome. Author(s): Dilts CV, Morris CA, Leonard CO. Source: Am J Med Genet Suppl. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2118772&query_hl=23&itool=pubmed_docsum
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I. The neurocognitive profile of Williams Syndrome: a complex pattern of strengths and weaknesses. Author(s): Bellugi U, Lichtenberger L, Jones W, Lai Z, St George M. Source: Journal of Cognitive Neuroscience. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10953231&query_hl=23&itool=pubmed_docsum
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Identification of genes from a 500-kb region at 7q11.23 that is commonly deleted in Williams syndrome patients. Author(s): Osborne LR, Martindale D, Scherer SW, Shi XM, Huizenga J, Heng HH, Costa T, Pober B, Lew L, Brinkman J, Rommens J, Koop B, Tsui LC. Source: Genomics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8812460&query_hl=23&itool=pubmed_docsum
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II. Hypersociability in Williams Syndrome. Author(s): Jones W, Bellugi U, Lai Z, Chiles M, Reilly J, Lincoln A, Adolphs R. Source: Journal of Cognitive Neuroscience. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10953232&query_hl=23&itool=pubmed_docsum
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III. Electrophysiological studies of face processing in Williams syndrome. Author(s): Mills DL, Alvarez TD, St George M, Appelbaum LG, Bellugi U, Neville H. Source: Journal of Cognitive Neuroscience. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10953233&query_hl=23&itool=pubmed_docsum
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Implicit learning in children and adults with Williams syndrome. Author(s): Don AJ, Schellenberg EG, Reber AS, DiGirolamo KM, Wang PP. Source: Developmental Neuropsychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12730025&query_hl=23&itool=pubmed_docsum
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Implicit versus explicit memory function in children with Down and Williams syndrome. Author(s): Vicari S. Source: Downs Syndr Res Pract. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11706810&query_hl=23&itool=pubmed_docsum
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Increased gyrification in Williams syndrome: evidence using 3D MRI methods. Author(s): Schmitt JE, Watts K, Eliez S, Bellugi U, Galaburda AM, Reiss AL. Source: Developmental Medicine and Child Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12033713&query_hl=23&itool=pubmed_docsum
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Increased local gyrification mapped in Williams syndrome. Author(s): Gaser C, Luders E, Thompson PM, Lee AD, Dutton RA, Geaga JA, Hayashi KM, Bellugi U, Galaburda AM, Korenberg JR, Mills DL, Toga AW, Reiss AL. Source: Neuroimage. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16901723&query_hl=23&itool=pubmed_docsum
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Increased prevalence of urinary symptoms and voiding dysfunction in Williams syndrome. Author(s): Schulman SL, Zderic S, Kaplan P. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8804343&query_hl=23&itool=pubmed_docsum
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Independence and adaptive behavior in adults with Williams syndrome. Author(s): Davies M, Howlin P, Udwin O. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9128941&query_hl=23&itool=pubmed_docsum
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In-depth analysis of spatial cognition in Williams syndrome: A critical assessment of the role of the LIMK1 gene. Author(s): Gray V, Karmiloff-Smith A, Funnell E, Tassabehji M. Source: Neuropsychologia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16216290&query_hl=23&itool=pubmed_docsum
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Infantile spasms in a patient with Williams syndrome and craniosynostosis. Author(s): Morimoto M, An B, Ogami A, Shin N, Sugino Y, Sawai Y, Usuku T, Tanaka M, Hirai K, Nishimura A, Hasegawa K, Sugimoto T. Source: Epilepsia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14636357&query_hl=23&itool=pubmed_docsum
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Infantile spasms in two children with Williams syndrome. Author(s): Tsao CY, Westman JA. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9215769&query_hl=23&itool=pubmed_docsum
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Inflectional morphology in German Williams syndrome. Author(s): Krause M, Penke M. Source: Brain and Cognition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12030478&query_hl=23&itool=pubmed_docsum
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Intact perception of biological motion in the face of profound spatial deficits: Williams syndrome. Author(s): Jordan H, Reiss JE, Hoffman JE, Landau B. Source: Psychological Science : a Journal of the American Psychological Society / Aps. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11934001&query_hl=23&itool=pubmed_docsum
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Interstitial deletion of chromosome 7q in a patient with Williams syndrome and infantile spasms. Author(s): Mizugishi K, Yamanaka K, Kuwajima K, Kondo I. Source: Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9747030&query_hl=23&itool=pubmed_docsum
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Interstitial deletion of the long arm of chromosome 6(q22.2q23) in a boy with phenotypic features of Williams syndrome. Author(s): Bzduch V, Lukacova M. Source: Clinical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2706804&query_hl=23&itool=pubmed_docsum
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Is everybody always my friend? Perception of approachability in Williams syndrome. Author(s): Frigerio E, Burt DM, Gagliardi C, Cioffi G, Martelli S, Perrett DI, Borgatti R. Source: Neuropsychologia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16005478&query_hl=23&itool=pubmed_docsum
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Ischemic stroke and intracranial multifocal cerebral arteriopathy in Williams syndrome. Author(s): Soper R, Chaloupka JC, Fayad PB, Greally JM, Shaywitz BA, Awad IA, Pober BR. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7776102&query_hl=23&itool=pubmed_docsum
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IV. Neuroanatomy of Williams syndrome: a high-resolution MRI study. Author(s): Reiss AL, Eliez S, Schmitt JE, Straus E, Lai Z, Jones W, Bellugi U. Source: Journal of Cognitive Neuroscience. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10953234&query_hl=23&itool=pubmed_docsum
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Knowledge enrichment and conceptual change in folkbiology: evidence from Williams syndrome. Author(s): Johnson SC, Carey S. Source: Cognitive Psychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9878105&query_hl=23&itool=pubmed_docsum
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Knowledge of constraints on compounding in children and adolescents with Williams syndrome. Author(s): Zukowski A. Source: Journal of Speech, Language, and Hearing Research : Jslhr. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15938061&query_hl=23&itool=pubmed_docsum
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Kyphoscoliosis in Williams syndrome. Author(s): Osebold WR, King HA. Source: Spine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7513444&query_hl=23&itool=pubmed_docsum
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Language and cognition in two children with Williams syndrome. Author(s): Thal D, Bates E, Bellugi U. Source: Journal of Speech and Hearing Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2476586&query_hl=23&itool=pubmed_docsum
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Language and conversational abilities in Williams syndrome: how good is good? Author(s): Stojanovik V, Perkins M, Howard S. Source: International Journal of Language & Communication Disorders / Royal College of Speech & Language Therapists. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11340788&query_hl=23&itool=pubmed_docsum
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Language and Williams syndrome: how intact is "intact"? Author(s): Karmiloff-Smith A, Grant J, Berthoud I, Davies M, Howlin P, Udwin O. Source: Child Development. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9180000&query_hl=23&itool=pubmed_docsum
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Language, speech and hearing in Williams syndrome: intervention approaches and research needs. Author(s): Meyerson MD, Frank RA. Source: Developmental Medicine and Child Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3582796&query_hl=23&itool=pubmed_docsum
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Large mirror movements of upper extremities in Williams syndrome. Author(s): Glos J, Bzduch V, Lisy L, Jariabkova K. Source: Pediatric Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8292223&query_hl=23&itool=pubmed_docsum
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Late onset stroke and myocardial infarction in Williams syndrome. Author(s): Blanc F, Wolff V, Talmant V, Attali P, Germain P, Flori E, Toutain A, Dollfus H, Tranchant C. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17116204&query_hl=23&itool=pubmed_docsum
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Learning to read in Williams syndrome: looking beneath the surface of atypical reading development. Author(s): Laing E, Hulme C, Grant J, Karmiloff-Smith A. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11583245&query_hl=23&itool=pubmed_docsum
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Lexical production in children with Williams syndrome: spontaneous use of gesture in a naming task. Author(s): Bello A, Capirci O, Volterra V. Source: Neuropsychologia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14644106&query_hl=23&itool=pubmed_docsum
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LIMK1 and CLIP-115: linking cytoskeletal defects to Williams syndrome. Author(s): Hoogenraad CC, Akhmanova A, Galjart N, De Zeeuw CI. Source: Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14745832&query_hl=23&itool=pubmed_docsum
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LIM-kinase deleted in Williams syndrome. Author(s): Tassabehji M, Metcalfe K, Fergusson WD, Carette MJ, Dore JK, Donnai D, Read AP, Proschel C, Gutowski NJ, Mao X, Sheer D. Source: Nature Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8673124&query_hl=23&itool=pubmed_docsum
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Linguistic abilities in Italian children with Williams syndrome. Author(s): Volterra V, Capirci O, Pezzini G, Sabbadini L, Vicari S. Source: Cortex. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8954245&query_hl=23&itool=pubmed_docsum
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Linguistic dissociations in Williams syndrome: evaluating receptive syntax in on-line and off-line tasks. Author(s): Karmiloff-Smith A, Tyler LK, Voice K, Sims K, Udwin O, Howlin P, Davies M. Source: Neuropsychologia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9665645&query_hl=23&itool=pubmed_docsum
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Longitudinal course of behavioral and emotional problems in Williams syndrome. Author(s): Einfeld SL, Tonge BJ, Rees VW. Source: Am J Ment Retard. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11246715&query_hl=23&itool=pubmed_docsum
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Longitudinal evaluation of growth, puberty, and bone maturation in children with Williams syndrome. Author(s): Partsch CJ, Dreyer G, Gosch A, Winter M, Schneppenheim R, Wessel A, Pankau R. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9880454&query_hl=23&itool=pubmed_docsum
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Love is. an abstract word: the influence of lexical semantics on verbal short-term memory in Williams syndrome. Author(s): Laing E, Grant J, Thomas M, Parmigiani C, Ewing S, Karmiloff-Smith A. Source: Cortex. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15714899&query_hl=23&itool=pubmed_docsum
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Low MSAFP levels and Williams syndrome. Author(s): Chodirker BN, Greenberg CR, Giddins NG, Dawson AJ, Evans JA, Chudley AE. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9375729&query_hl=23&itool=pubmed_docsum
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Masseter spasm in Williams syndrome. Author(s): Matthews AJ, Vernon JM. Source: Anaesthesia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1888003&query_hl=23&itool=pubmed_docsum
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Mechanical properties of the common carotid artery in Williams syndrome. Author(s): Aggoun Y, Sidi D, Levy BI, Lyonnet S, Kachaner J, Bonnet D. Source: Heart (British Cardiac Society). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10956293&query_hl=23&itool=pubmed_docsum
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Medial telangiectatic sacral nevi (Types A and C) associated with Williams syndrome. Author(s): Schepis C, Greco D, Bosco P, Ragusa A, Romano C. Source: Dermatology (Basel, Switzerland). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11096215&query_hl=23&itool=pubmed_docsum
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Medical considerations in dental treatment of children with Williams syndrome. Author(s): Moskovitz M, Brener D, Faibis S, Peretz B. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15829880&query_hl=23&itool=pubmed_docsum
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Memory abilities in children with Williams syndrome. Author(s): Vicari S, Brizzolara D, Carlesimo GA, Pezzini G, Volterra V. Source: Cortex. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8886525&query_hl=23&itool=pubmed_docsum
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Metacarpophalangeal pattern profile analysis in Williams syndrome. Author(s): Burns MA, McLeod DR, Linton LR, Butler MG. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8256807&query_hl=23&itool=pubmed_docsum
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Micro-deletion detected by fluorescent in situ hybridization for Williams syndrome. Author(s): Dewan K, Borgaonkar DS, Bartoshesky LE, Tuttle D. Source: Del Med J. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10615798&query_hl=23&itool=pubmed_docsum
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Microdeletion oe chromosomal region 7Q11.23 in Williams syndrome. Author(s): Hou JW, Wang JK, Wang TR. Source: J Formos Med Assoc. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9071842&query_hl=23&itool=pubmed_docsum
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Molecular cytogenetic diagnosis of Williams syndrome. Author(s): Hirota H, Matsuoka R, Kimura M, Imamura S, Joh-o K, Ando M, Takao A, Momma K. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8862624&query_hl=23&itool=pubmed_docsum
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Molecular definition of the chromosome 7 deletion in Williams syndrome and parentof-origin effects on growth. Author(s): Perez Jurado LA, Peoples R, Kaplan P, Hamel BC, Francke U. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8808592&query_hl=23&itool=pubmed_docsum
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Morphological abilities of Hebrew-speaking adolescents with Williams syndrome. Author(s): Levy Y, Hermon S. Source: Developmental Neuropsychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12730020&query_hl=23&itool=pubmed_docsum
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Morphological patterns in Hungarian children with Williams syndrome and the rule debates. Author(s): Pleh C, Lukacs A, Racsmany M. Source: Brain and Language. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12972368&query_hl=23&itool=pubmed_docsum
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Morphology and morphometry of the corpus callosum in Williams syndrome: a T1weighted MRI study. Author(s): Tomaiuolo F, Di Paola M, Caravale B, Vicari S, Petrides M, Caltagirone C. Source: Neuroreport. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12488811&query_hl=23&itool=pubmed_docsum
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Motion processing specialization in Williams syndrome. Author(s): Reiss JE, Hoffman JE, Landau B. Source: Vision Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16005929&query_hl=23&itool=pubmed_docsum
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Mucinous cystadenoma of ovary in a patient with Williams syndrome. Author(s): Marles SL, Goldberg NA, Chudley AE. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8488885&query_hl=23&itool=pubmed_docsum
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Multifocal intracranial occlusive vasculopathy resulting in stroke: an unusual manifestation of Williams syndrome. Author(s): Putman CM, Chaloupka JC, Eklund JE, Fulbright RK. Source: Ajnr. American Journal of Neuroradiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7484650&query_hl=23&itool=pubmed_docsum
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Multiple object tracking in people with Williams syndrome and in normally developing children. Author(s): O'Hearn K, Landau B, Hoffman JE. Source: Psychological Science : a Journal of the American Psychological Society / Aps. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16262778&query_hl=23&itool=pubmed_docsum
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Multisystem study of 20 older adults with Williams syndrome. Author(s): Cherniske EM, Carpenter TO, Klaiman C, Young E, Bregman J, Insogna K, Schultz RT, Pober BR. Source: Am J Med Genet A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15534874&query_hl=23&itool=pubmed_docsum
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Musical behavior in a neurogenetic developmental disorder: evidence from Williams Syndrome. Author(s): Levitin DJ. Source: Annals of the New York Academy of Sciences. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16597782&query_hl=23&itool=pubmed_docsum
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Natural history of Williams syndrome: physical characteristics. Author(s): Morris CA, Demsey SA, Leonard CO, Dilts C, Blackburn BL. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2456379&query_hl=23&itool=pubmed_docsum
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Neonatal Williams syndrome presenting as an isolated supravalvular pulmonary stenosis. Author(s): di Gioia CR, Ciallella C, d'Amati G, Parroni E, Nardone AM, Gallo P. Source: Archives of Pathology & Laboratory Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12946215&query_hl=23&itool=pubmed_docsum
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Neural basis of genetically determined visuospatial construction deficit in Williams syndrome. Author(s): Meyer-Lindenberg A, Kohn P, Mervis CB, Kippenhan JS, Olsen RK, Morris CA, Berman KF. Source: Neuron. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15339645&query_hl=23&itool=pubmed_docsum
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Neural correlates of auditory perception in Williams syndrome: an fMRI study. Author(s): Levitin DJ, Menon V, Schmitt JE, Eliez S, White CD, Glover GH, Kadis J, Korenberg JR, Bellugi U, Reiss AL. Source: Neuroimage. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12507445&query_hl=23&itool=pubmed_docsum
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Neural correlates of genetically abnormal social cognition in Williams syndrome. Author(s): Meyer-Lindenberg A, Hariri AR, Munoz KE, Mervis CB, Mattay VS, Morris CA, Berman KF. Source: Nature Neuroscience. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16007084&query_hl=23&itool=pubmed_docsum
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Neural mechanisms in Williams syndrome: a unique window to genetic influences on cognition and behaviour. Author(s): Meyer-Lindenberg A, Mervis CB, Berman KF. Source: Nature Reviews. Neuroscience. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16760918&query_hl=23&itool=pubmed_docsum
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Neurobiological models of visuospatial cognition in children with Williams syndrome: measures of dorsal-stream and frontal function. Author(s): Atkinson J, Braddick O, Anker S, Curran W, Andrew R, Wattam-Bell J, Braddick F. Source: Developmental Neuropsychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12730023&query_hl=23&itool=pubmed_docsum
76
Williams Syndrome
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Neurocranial morphology and growth in Williams syndrome. Author(s): Axelsson S, Kjaer I, Heiberg A, Bjornland T, Storhaug K. Source: European Journal of Orthodontics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15743861&query_hl=23&itool=pubmed_docsum
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Neurologic findings in children and adults with Williams syndrome. Author(s): Chapman CA, du Plessis A, Pober BR. Source: Journal of Child Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8745391&query_hl=23&itool=pubmed_docsum
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Neuropsychological profile of Italians with Williams syndrome: an example of a dissociation between language and cognition? Author(s): Vicari S, Bates E, Caselli MC, Pasqualetti P, Gagliardi C, Tonucci F, Volterra V. Source: Journal of the International Neuropsychological Society : Jins. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15637777&query_hl=23&itool=pubmed_docsum
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Neuropsychological, neurological, and neuroanatomical profile of Williams syndrome. Author(s): Bellugi U, Bihrle A, Jernigan T, Trauner D, Doherty S. Source: Am J Med Genet Suppl. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2144426&query_hl=23&itool=pubmed_docsum
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New case of thyroid dysgenesis and clinical signs of hypothyroidism in Williams syndrome. Author(s): Bini R, Pela I. Source: Am J Med Genet A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15108207&query_hl=23&itool=pubmed_docsum
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Non-Hodgkin lymphoma in a child with Williams syndrome. Author(s): Amenta S, Moschovi M, Sofocleous C, Kostaridou S, Mavrou A, Fryssira H. Source: Cancer Genetics and Cytogenetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15381380&query_hl=23&itool=pubmed_docsum
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Object recognition with severe spatial deficits in Williams syndrome: sparing and breakdown. Author(s): Landau B, Hoffman JE, Kurz N. Source: Cognition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16185678&query_hl=23&itool=pubmed_docsum
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Objects, motions, and paths: spatial language in children with Williams syndrome. Author(s): Landau B, Zukowski A. Source: Developmental Neuropsychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12730022&query_hl=23&itool=pubmed_docsum
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Occurrence of an astrocytoma in a patient with Williams syndrome. Author(s): Semmekrot BA, Rotteveel JJ, Bakker-Niezen SH, Logt F. Source: Pediatr Neurosci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3843262&query_hl=23&itool=pubmed_docsum
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Occurrence of non-Hodgkin's lymphoma in Williams syndrome--case report. Author(s): Felice PV, Ritter SD, Anto J. Source: Angiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8129194&query_hl=23&itool=pubmed_docsum
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Oligoyric microcephaly in a child with Williams syndrome. Author(s): Faravelli F, D'Arrigo S, Bagnasco I, Selicorni A, D'Incerti L, Riva D, Pantaleoni C. Source: Am J Med Genet A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12567416&query_hl=23&itool=pubmed_docsum
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On the AJR digital viewbox. Bilateral pulmonary sequestration with bridging isthmus in a boy with Williams syndrome. Author(s): Kuo R, Shih SL, Huang JK. Source: Ajr. American Journal of Roentgenology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16794131&query_hl=23&itool=pubmed_docsum
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On the trail of genetic culprits in Williams syndrome. Author(s): Keating MT. Source: Cardiovascular Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9463625&query_hl=23&itool=pubmed_docsum
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Orientation coding: a specific deficit in Williams syndrome? Author(s): Farran EK. Source: Developmental Neuropsychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16671858&query_hl=23&itool=pubmed_docsum
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Outcome in adult life for people with Williams syndrome-- results from a survey of 239 families. Author(s): Howlin P, Udwin O. Source: Journal of Intellectual Disability Research : Jidr. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16403203&query_hl=23&itool=pubmed_docsum
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Parieto-occipital grey matter abnormalities in children with Williams syndrome. Author(s): Boddaert N, Mochel F, Meresse I, Seidenwurm D, Cachia A, Brunelle F, Lyonnet S, Zilbovicius M. Source: Neuroimage. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16380272&query_hl=23&itool=pubmed_docsum
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People with Williams syndrome process faces holistically. Author(s): Tager-Flusberg H, Plesa-Skwerer D, Faja S, Joseph RM. Source: Cognition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12893122&query_hl=23&itool=pubmed_docsum
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Perceiving facial and vocal expressions of emotion in individuals with Williams syndrome. Author(s): Plesa-Skwerer D, Faja S, Schofield C, Verbalis A, Tager-Flusberg H. Source: Am J Ment Retard. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16332153&query_hl=23&itool=pubmed_docsum
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Perceptual grouping ability in Williams syndrome: evidence for deviant patterns of performance. Author(s): Farran EK. Source: Neuropsychologia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15721194&query_hl=23&itool=pubmed_docsum
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Periodic limb movement in sleep in children with Williams syndrome. Author(s): Arens R, Wright B, Elliott J, Zhao H, Wang PP, Brown LW, Namey T, Kaplan P. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9821427&query_hl=23&itool=pubmed_docsum
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Perioperative care of the patient with Williams syndrome. Author(s): Medley J, Russo P, Tobias JD. Source: Paediatric Anaesthesia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15725324&query_hl=23&itool=pubmed_docsum
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Periventricular nodular heterotopia and Williams syndrome. Author(s): Ferland RJ, Gaitanis JN, Apse K, Tantravahi U, Walsh CA, Sheen VL. Source: Am J Med Genet A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16691586&query_hl=23&itool=pubmed_docsum
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Personality characteristics and behaviour problems in individuals of different ages with Williams syndrome. Author(s): Gosch A, Pankau R. Source: Developmental Medicine and Child Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9295848&query_hl=23&itool=pubmed_docsum
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Phosphoserine phosphatase deficiency in a patient with Williams syndrome. Author(s): Jaeken J, Detheux M, Fryns JP, Collet JF, Alliet P, Van Schaftingen E. Source: Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9222972&query_hl=23&itool=pubmed_docsum
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PMS2-related genes flank the rearrangement breakpoints associated with Williams syndrome and other diseases on human chromosome 7. Author(s): Osborne LR, Herbrick JA, Greavette T, Heng HH, Tsui LC, Scherer SW. Source: Genomics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9344666&query_hl=23&itool=pubmed_docsum
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Portal hypertension in Williams syndrome: report of two patients. Author(s): Casanelles Mdel C, Gil-Fernandez JJ, Casero LF, Bengoechea MG, Serrano R, Ranada JM, Jurado LA. Source: Am J Med Genet A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12687671&query_hl=23&itool=pubmed_docsum
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Post-natal size and morphology of the sella turcica in Williams syndrome. Author(s): Axelsson S, Storhaug K, Kjaer I. Source: European Journal of Orthodontics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15650071&query_hl=23&itool=pubmed_docsum
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Pragmatic language impairment and social deficits in Williams syndrome: a comparison with Down's syndrome and specific language impairment. Author(s): Laws G, Bishop D. Source: International Journal of Language & Communication Disorders / Royal College of Speech & Language Therapists. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14660186&query_hl=23&itool=pubmed_docsum
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Precocious puberty in a Williams syndrome patient. Author(s): Douchi T, Maruta K, Kuwahata R, Nagata Y. Source: Obstetrics and Gynecology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10546771&query_hl=23&itool=pubmed_docsum
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Prevalence estimation of Williams syndrome. Author(s): Stromme P, Bjornstad PG, Ramstad K. Source: Journal of Child Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12088082&query_hl=23&itool=pubmed_docsum
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Prevalence of psychiatric disorders in 4 to 16-year-olds with Williams syndrome. Author(s): Leyfer OT, Woodruff-Borden J, Klein-Tasman BP, Fricke JS, Mervis CB. Source: Am J Med Genet B Neuropsychiatr Genet. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16823805&query_hl=23&itool=pubmed_docsum
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Probed serial recall in Williams syndrome: lexical influences on phonological shortterm memory. Author(s): Brock J, McCormack T, Boucher J. Source: Journal of Speech, Language, and Hearing Research : Jslhr. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15989398&query_hl=23&itool=pubmed_docsum
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Procedural learning deficit in children with Williams syndrome. Author(s): Vicari S, Bellucci S, Carlesimo GA. Source: Neuropsychologia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11311297&query_hl=23&itool=pubmed_docsum
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Progressive left main coronary artery obstruction leading to myocardial infarction in a child with Williams syndrome. Author(s): Bonnet D, Cormier V, Villain E, Bonhoeffer P, Kachaner J. Source: European Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9365061&query_hl=23&itool=pubmed_docsum
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Pseudohypertension and Williams syndrome. Author(s): Bastianon V. Source: Pediatric Cardiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8833503&query_hl=23&itool=pubmed_docsum
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Radioulnar synostosis in Williams syndrome. Author(s): Bzduch V, Spissak L. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2738785&query_hl=23&itool=pubmed_docsum
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Radio-ulnar synostosis in Williams syndrome. A frequently associated anomaly. Author(s): Charvat KA, Hornstein L, Oestreich AE. Source: Pediatric Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1771116&query_hl=23&itool=pubmed_docsum
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Radioulnar synostosis in Williams syndrome: a historical overview. Author(s): Bzduch V. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8209922&query_hl=23&itool=pubmed_docsum
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Reading and phonological awareness in Williams syndrome. Author(s): Menghini D, Verucci L, Vicari S. Source: Neuropsychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14744185&query_hl=23&itool=pubmed_docsum
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Reading the windows to the soul: evidence of domain-specific sparing in Williams syndrome. Author(s): Tager-Flusberg H, Boshart J, Baron-Cohen S. Source: Journal of Cognitive Neuroscience. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9802996&query_hl=23&itool=pubmed_docsum
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Reduced stereoacuity in Williams syndrome. Author(s): Sadler LS, Olitsky SE, Reynolds JD. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8985489&query_hl=23&itool=pubmed_docsum
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Refinement of the genomic structure of STX1A and mutation analysis in nondeletion Williams syndrome patients. Author(s): Wu YQ, Bejjani BA, Tsui LC, Mandel A, Osborne LR, Shaffer LG. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11977160&query_hl=23&itool=pubmed_docsum
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Relative sparing of primary auditory cortex in Williams Syndrome. Author(s): Holinger DP, Bellugi U, Mills DL, Korenberg JR, Reiss AL, Sherman GF, Galaburda AM. Source: Brain Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15777750&query_hl=23&itool=pubmed_docsum
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Renal abnormalities associated with Williams syndrome. Author(s): Suzuki Y, Shimazaki S, Kaneko K, Ino T, Yabuta K. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1403410&query_hl=23&itool=pubmed_docsum
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Renal findings in 40 individuals with Williams syndrome. Author(s): Pober BR, Lacro RV, Rice C, Mandell V, Teele RL. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8488870&query_hl=23&itool=pubmed_docsum
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Renal insufficiency in Williams syndrome. Author(s): Biesecker LG, Laxova R, Friedman A. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3314505&query_hl=23&itool=pubmed_docsum
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Repetition priming in adults with Williams syndrome: age-related dissociation between implicit and explicit memory. Author(s): Krinsky-McHale SJ, Kittler P, Brown WT, Jenkins EC, Devenny DA. Source: Am J Ment Retard. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16212450&query_hl=23&itool=pubmed_docsum
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Restenosis and pseudoaneurysm formation after stent placement for aortic coarctation in Williams syndrome. Author(s): Apostolopoulou SC, Kelekis NL, Laskari C, Kaklamanis L, Rammos S. Source: Journal of Vascular and Interventional Radiology : Jvir. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11997368&query_hl=23&itool=pubmed_docsum
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Review of referrals for the FISH detection of Williams syndrome highlights the importance of testing in supravalvular aortic stenosis/pulmonary stenosis. Author(s): St Heaps L, Robson L, Smith A. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11428332&query_hl=23&itool=pubmed_docsum
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Rickets in an infant with Williams syndrome. Author(s): Mathias RS. Source: Pediatric Nephrology (Berlin, Germany). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10872191&query_hl=23&itool=pubmed_docsum
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Rieger's and Williams syndrome. A rare clinical case. Author(s): Balacco-Gabrieli C, Lorusso VV, La Torre M. Source: Ophthalmic Paediatr Genet. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=4094730&query_hl=23&itool=pubmed_docsum
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Second-order belief attribution in Williams syndrome: intact or impaired? Author(s): Sullivan K, Tager-Flusberg H. Source: Am J Ment Retard. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10587733&query_hl=23&itool=pubmed_docsum
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Sedation for Magnetic Resonance Imaging in a child affected with Williams syndrome. Author(s): Baldinelli F, DeCarli A, Accinelli G. Source: Minerva Anestesiol. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12792585&query_hl=23&itool=pubmed_docsum
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Self concept in people with Williams syndrome and Prader-Willi syndrome. Author(s): Plesa-Skwerer D, Sullivan K, Joffre K, Tager-Flusberg H. Source: Research in Developmental Disabilities. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15026090&query_hl=23&itool=pubmed_docsum
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Sensorineural hearing loss in children and adults with Williams syndrome. Author(s): Marler JA, Elfenbein JL, Ryals BM, Urban Z, Netzloff ML. Source: Am J Med Genet A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16222677&query_hl=23&itool=pubmed_docsum
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Serum NGF levels in children and adolescents with either Williams syndrome or Down syndrome. Author(s): Calamandrei G, Alleva E, Cirulli F, Queyras A, Volterra V, Capirci O, Vicari S, Giannotti A, Turrini P, Aloe L. Source: Developmental Medicine and Child Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11104346&query_hl=23&itool=pubmed_docsum
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Severe colonic diverticulitis in an adolescent with Williams syndrome. Author(s): Deshpande AV, Oliver M, Yin M, Goh TH, Hutson JM. Source: Journal of Paediatrics and Child Health. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16398877&query_hl=23&itool=pubmed_docsum
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Severe coronary artery disease in the absence of supravalvular stenosis in a patient with Williams syndrome. Author(s): van Pelt NC, Wilson NJ, Lear G. Source: Pediatric Cardiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15549615&query_hl=23&itool=pubmed_docsum
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Severe infantile hypercalcemia associated with Williams syndrome successfully treated with intravenously administered pamidronate. Author(s): Cagle AP, Waguespack SG, Buckingham BA, Shankar RR, Dimeglio LA. Source: Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15466114&query_hl=23&itool=pubmed_docsum
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Shifting attention and joint attention dissociation in Williams syndrome: implications for the cerebellum and social deficits in autism. Author(s): Lincoln A, Lai Z, Jones W. Source: Neurocase : Case Studies in Neuropsychology, Neuropsychiatry, and Behavioural Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12119319&query_hl=23&itool=pubmed_docsum
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Short-term longitudinal study of a child with Williams syndrome. Author(s): Stojanovik V, James D. Source: International Journal of Language & Communication Disorders / Royal College of Speech & Language Therapists. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16546896&query_hl=23&itool=pubmed_docsum
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Single signal of the Williams syndrome chromosome region 1 gene in hyperploidic bone marrow cells of acute lymphoblastic leukemia in a Williams syndrome patient. Author(s): Culic V, Culic S, Armanda V, Resic B, Lasan R, Peterlin B. Source: Medical and Pediatric Oncology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11836725&query_hl=23&itool=pubmed_docsum
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Skin elastic fibers in Williams syndrome. Author(s): Dridi SM, Ghomrasseni S, Bonnet D, Aggoun Y, Vabres P, Bodemer C, Lyonnet S, de Prost Y, Fraitag S, Pellat B, Sidi D, Godeau G. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10533027&query_hl=23&itool=pubmed_docsum
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Spatial breakdown in spatial construction: evidence from eye fixations in children with Williams syndrome. Author(s): Hoffman JE, Landau B, Pagani B. Source: Cognitive Psychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12694695&query_hl=23&itool=pubmed_docsum
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Spatial representation and attention in toddlers with Williams syndrome and Down syndrome. Author(s): Brown JH, Johnson MH, Paterson SJ, Gilmore R, Longhi E, Karmiloff-Smith A. Source: Neuropsychologia. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12667539&query_hl=23&itool=pubmed_docsum
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Spontaneous regression of peripheral pulmonary artery stenosis in Williams syndrome. Author(s): Miyamura H, Watanabe H, Tatebe S, Eguchi S. Source: Japanese Circulation Journal. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8803725&query_hl=23&itool=pubmed_docsum
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Sudden death of a 21-year-old female with Williams syndrome showing rare complications. Author(s): Imashuku S, Hayashi S, Kuriyama K, Hibi S, Tabata Y, Todo S. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10881597&query_hl=23&itool=pubmed_docsum
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Supravalvular aortic stenosis without Williams syndrome. Author(s): Ozergin U, Sunam GS, Yeniterzi M, Yuksek T, Solak T, Solak H. Source: The Thoracic and Cardiovascular Surgeon. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8896169&query_hl=23&itool=pubmed_docsum
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Supravalvular aortic stenosis, Williams syndrome and sudden death. A case report. Author(s): Suarez-Mier MP, Morentin B. Source: Forensic Science International. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10629967&query_hl=23&itool=pubmed_docsum
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Symmetry of cortical folding abnormalities in Williams syndrome revealed by surface-based analyses. Author(s): Van Essen DC, Dierker D, Snyder AZ, Raichle ME, Reiss AL, Korenberg J. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16707799&query_hl=23&itool=pubmed_docsum
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The magnetoencephalographic response to upright and inverted face stimuli in a patient with Williams syndrome. Author(s): Nakamura M, Watanabe S, Gunji A, Kakigi R. Source: Pediatric Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16648006&query_hl=23&itool=pubmed_docsum
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The neurobiology of Williams syndrome: cascading influences of visual system impairment? Author(s): Eckert MA, Galaburda AM, Mills DL, Bellugi U, Korenberg JR, Reiss AL. Source: Cellular and Molecular Life Sciences : Cmls. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16810457&query_hl=23&itool=pubmed_docsum
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The visual regulation of goal-directed reaching movements in adults with Williams syndrome, Down syndrome, and other developmental delays. Author(s): Elliott D, Welsh TN, Lyons J, Hansen S, Wu M. Source: Motor Control. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16571907&query_hl=23&itool=pubmed_docsum
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The Williams syndrome transcription factor interacts with PCNA to target chromatin remodelling by ISWI to replication foci. Author(s): Poot RA, Bozhenok L, van den Berg DL, Steffensen S, Ferreira F, Grimaldi M, Gilbert N, Ferreira J, Varga-Weisz PD. Source: Nature Cell Biology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15543136&query_hl=23&itool=pubmed_docsum
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Thoracolumbar syrinx in association with Williams syndrome. Author(s): Cohen DB, Quigley MR. Source: Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16831893&query_hl=23&itool=pubmed_docsum
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Thyroid anomalies in Williams syndrome: investigation of 95 patients. Author(s): Selicorni A, Fratoni A, Pavesi MA, Bottigelli M, Arnaboldi E, Milani D. Source: Am J Med Genet A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16596673&query_hl=23&itool=pubmed_docsum
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Thyroid function and morphology in patients affected by Williams syndrome. Author(s): Stagi S, Bindi G, Neri AS, Lapi E, Losi S, Jenuso R, Salti R, Chiarelli F. Source: Clinical Endocrinology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16181239&query_hl=23&itool=pubmed_docsum
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Thyroid morphology and subclinical hypothyroidism in children and adolescents with Williams syndrome. Author(s): Cambiaso P, Orazi C, Digilio MC, Loche S, Capolino R, Tozzi A, Faedda A, Cappa M. Source: The Journal of Pediatrics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17188616&query_hl=23&itool=pubmed_docsum
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To modulate or not to modulate: differing results in uniquely shaped Williams syndrome brains. Author(s): Eckert MA, Tenforde A, Galaburda AM, Bellugi U, Korenberg JR, Mills D, Reiss AL. Source: Neuroimage. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16806978&query_hl=23&itool=pubmed_docsum
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Two pregnancies in a woman with Williams syndrome. Author(s): Mulik VV, Temple KI, Howe DT. Source: Bjog : an International Journal of Obstetrics and Gynaecology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15104621&query_hl=23&itool=pubmed_docsum
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Unbalanced 13;18 translocation and Williams syndrome. Author(s): Colley A, Thakker Y, Ward H, Donnai D. Source: Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1552549&query_hl=23&itool=pubmed_docsum
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Unifocalization of the neck arteries combined with aortic arch replacement for Williams syndrome. Author(s): Yamada Y, Yamagishi M, Shuntoh K, Okano T, Hayashida K, Shinkawa T, Kitamura N. Source: The Journal of Thoracic and Cardiovascular Surgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11882841&query_hl=23&itool=pubmed_docsum
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Unusual cognitive and behavioural profile in a Williams syndrome patient with atypical 7q11.23 deletion. Author(s): Gagliardi C, Bonaglia MC, Selicorni A, Borgatti R, Giorda R. Source: Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12843326&query_hl=23&itool=pubmed_docsum
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V. Multi-level analysis of cortical neuroanatomy in Williams syndrome. Author(s): Galaburda AM, Bellugi U. Source: Journal of Cognitive Neuroscience. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10953235&query_hl=23&itool=pubmed_docsum
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Variability of the cranial and dental phenotype in Williams syndrome. Author(s): Axelsson S. Source: Swed Dent J Suppl. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15762376&query_hl=23&itool=pubmed_docsum
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VI. Genome structure and cognitive map of Williams syndrome. Author(s): Korenberg JR, Chen XN, Hirota H, Lai Z, Bellugi U, Burian D, Roe B, Matsuoka R. Source: Journal of Cognitive Neuroscience. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10953236&query_hl=23&itool=pubmed_docsum
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Visual and spatial working memory dissociation: evidence from Williams syndrome. Author(s): Vicari S, Bellucci S, Carlesimo GA. Source: Developmental Medicine and Child Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12647929&query_hl=23&itool=pubmed_docsum
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Visual and visuospatial development in young children with Williams syndrome. Author(s): Atkinson J, Anker S, Braddick O, Nokes L, Mason A, Braddick F. Source: Developmental Medicine and Child Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11368486&query_hl=23&itool=pubmed_docsum
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Visual information process in Williams syndrome: intact motion detection accompanied by typical visuospatial dysfunctions. Author(s): Nakamura M, Kaneoke Y, Watanabe K, Kakigi R. Source: The European Journal of Neuroscience. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12431234&query_hl=23&itool=pubmed_docsum
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Visual search in typically developing toddlers and toddlers with Fragile X or Williams syndrome. Author(s): Scerif G, Cornish K, Wilding J, Driver J, Karmiloff-Smith A. Source: Dev Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15323123&query_hl=23&itool=pubmed_docsum
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Visuo-spatial and linguistic abilities in a twin with Williams syndrome. Author(s): Volterra V, Longobardi E, Pezzini G, Vicari S, Antenore C. Source: Journal of Intellectual Disability Research : Jidr. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10466868&query_hl=23&itool=pubmed_docsum
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Visuospatial cognition in Williams syndrome: reviewing and accounting for the strengths and weaknesses in performance. Author(s): Farran EK, Jarrold C. Source: Developmental Neuropsychology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12730024&query_hl=23&itool=pubmed_docsum
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Vocal cord abnormalities in Williams syndrome: a further manifestation of elastin deficiency. Author(s): Vaux KK, Wojtczak H, Benirschke K, Jones KL. Source: Am J Med Genet A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12784297&query_hl=23&itool=pubmed_docsum
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What can developmental disorders tell us about the neurocomputational constraints that shape development? The case of Williams syndrome. Author(s): Karmiloff-Smith A, Thomas M. Source: Development and Psychopathology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14984134&query_hl=23&itool=pubmed_docsum
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Williams syndrome and deficiency in visuospatial recognition. Author(s): Nakamura M, Watanabe K, Matsumoto A, Yamanaka T, Kumagai T, Miyazaki S, Matsushima M, Mita K. Source: Developmental Medicine and Child Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11570631&query_hl=23&itool=pubmed_docsum
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Williams syndrome and happiness. Author(s): Levine K, Wharton R. Source: Am J Ment Retard. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11008844&query_hl=23&itool=pubmed_docsum
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Williams syndrome and related disorders. Author(s): Morris CA, Mervis CB. Source: Annual Review of Genomics and Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11701637&query_hl=23&itool=pubmed_docsum
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Williams syndrome associated with Crohn disease, multiple infections, and chronic granulomatous disease. Author(s): Gilbert-Barness E, Fox T, Morrow G, Luquette M, Pomerance HH. Source: Fetal Pediatr Pathol. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15371121&query_hl=23&itool=pubmed_docsum
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Williams syndrome deficits in visual spatial processing linked to GTF2IRD1 and GTF2I on chromosome 7q11.23. Author(s): Hirota H, Matsuoka R, Chen XN, Salandanan LS, Lincoln A, Rose FE, Sunahara M, Osawa M, Bellugi U, Korenberg JR. Source: Genetics in Medicine : Official Journal of the American College of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12865760&query_hl=23&itool=pubmed_docsum
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Williams syndrome: from genotype through to the cognitive phenotype. Author(s): Donnai D, Karmiloff-Smith A. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11180224&query_hl=23&itool=pubmed_docsum
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Williams syndrome: pediatric, neurologic, and cognitive development. Author(s): Carrasco X, Castillo S, Aravena T, Rothhammer P, Aboitiz F. Source: Pediatric Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15730896&query_hl=23&itool=pubmed_docsum
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Word reading and reading-related skills in adolescents with Williams syndrome. Author(s): Levy Y, Smith J, Tager-Flusberg H. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12751849&query_hl=23&itool=pubmed_docsum
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Word reading and reading-related skills in Hebrew-speaking adolescents with Williams syndrome. Author(s): Levy Y, Antebi V. Source: Neurocase : Case Studies in Neuropsychology, Neuropsychiatry, and Behavioural Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15788284&query_hl=23&itool=pubmed_docsum
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CHAPTER 2. ALTERNATIVE MEDICINE AND WILLIAMS SYNDROME Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Williams syndrome. At the conclusion of this chapter, we will provide additional sources.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to Williams syndrome and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select CAM on PubMed. Enter Williams syndrome (or synonyms) into the search box. Click Go. The following references provide information on particular aspects of complementary and alternative medicine that are related to Williams syndrome: •
Adjunct diagnostic test for Angelman syndrome: the tuning fork response. Author(s): Hall BD. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11977186&query_hl=1&itool=pubmed_docsum
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Assessment of dietary vitamin D requirements during pregnancy and lactation. Author(s): Hollis BW, Wagner CL. Source: The American Journal of Clinical Nutrition. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15113709&query_hl=1&itool=pubmed_docsum
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Autism as a neurodevelopmental disorder affecting communication and learning in early childhood: prenatal origins, post-natal course and effective educational support. Author(s): Trevarthen C.
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Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10970712&query_hl=1&itool=pubmed_docsum •
Block design performance in the Williams syndrome phenotype: a problem with mental imagery? Author(s): Farran EK, Jarrold C, Gathercole SE. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11583244&query_hl=1&itool=pubmed_docsum
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Delineation of facial archetypes by 3d averaging. Author(s): Shaweesh AI, Thomas CD, Bankier A, Clement JG. Source: Ann R Australas Coll Dent Surg. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16479861&query_hl=1&itool=pubmed_docsum
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Early categorization abilities in young children with Williams syndrome. Author(s): Nazzi T, Karmiloff-Smith A. Source: Neuroreport. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12151782&query_hl=1&itool=pubmed_docsum
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Evidence from two genetic syndromes for the independence of spatial and visual working memory. Author(s): Vicari S, Bellucci S, Carlesimo GA. Source: Developmental Medicine and Child Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16417668&query_hl=1&itool=pubmed_docsum
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Genetics and cardiac anomalies: the heart of the matter. Author(s): Prasad C, Chudley AE. Source: Indian J Pediatr. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12019554&query_hl=1&itool=pubmed_docsum
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Global and local music perception in children with Williams syndrome. Author(s): Deruelle C, Schon D, Rondan C, Mancini J. Source: Neuroreport. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15812322&query_hl=1&itool=pubmed_docsum
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Huldre folk of elfame: a case of hidden infirmities. Author(s): Weber KT. Source: Cardiovascular Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9463624&query_hl=1&itool=pubmed_docsum
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Hyperacusis in Williams syndrome: characteristics and associated neuroaudiologic abnormalities. Author(s): Gothelf D, Farber N, Raveh E, Apter A, Attias J. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16476938&query_hl=1&itool=pubmed_docsum
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Music and anxiety in Williams syndrome: a harmonious or discordant relationship? Author(s): Dykens EM, Rosner BA, Ly T, Sagun J. Source: Am J Ment Retard. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16080773&query_hl=1&itool=pubmed_docsum
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Treatment of hyperacusis in Williams syndrome with bilateral conductive hearing loss. Author(s): Miani C, Passon P, Bracale AM, Barotti A, Panzolli N. Source: European Archives of Oto-Rhino-Laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (Eufos) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11699823&query_hl=1&itool=pubmed_docsum
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://health.aol.com/healthyliving/althealth
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Chinese Medicine: http://www.newcenturynutrition.com/
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Alternative/
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 3. BOOKS ON WILLIAMS SYNDROME Overview This chapter provides bibliographic book references relating to Williams syndrome. In addition to online booksellers such as www.amazon.com and www.bn.com, the National Library of Medicine is an excellent source for book titles on Williams syndrome. Your local medical library also may have these titles available for loan.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for Williams syndrome at online booksellers’ Web sites, you may discover non-medical books that use the generic term “Williams syndrome” (or a synonym) in their titles. The following is indicative of the results you might find when searching for Williams syndrome (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Autism and Williams Syndrome (Essays in Developmental Psychology) TagerFlusberg (2007); ISBN: 1841690082; http://www.amazon.com/exec/obidos/ASIN/1841690082/icongroupinterna
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Behavioral phenotypes and special education: Parent report of educational issues for children with Down syndrome, Prader-Willi syndrome, and Williams syndrome. from: The Journal of Special Education Deborah J Fidler, Robert M Hodapp, and Elisabeth M Dykens (2005); ISBN: B000BE2JOU; http://www.amazon.com/exec/obidos/ASIN/B000BE2JOU/icongroupinterna
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Characteristics and education of the young child with Williams syndrome Candace L Engelmann (1993); ISBN: B0006P28O0; http://www.amazon.com/exec/obidos/ASIN/B0006P28O0/icongroupinterna
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Evidence for unusual spatial location coding in Williams syndrome: An explanation for the local bias in visuo-spatial construction tasks? E.K. Farran and C. Jarrold; ISBN:
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B000MAHOBG; http://www.amazon.com/exec/obidos/ASIN/B000MAHOBG/icongroupinterna •
Fears, hyperacusis and musicality in Williams syndrome S. Blomberg, M. Rosander, and G. Andersson; ISBN: B000LKA1GC; http://www.amazon.com/exec/obidos/ASIN/B000LKA1GC/icongroupinterna
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Fulfilling dreams: A handbook for parents of people with Williams Syndrome Barbara Scheiber (2002); ISBN: B0006S01EQ; http://www.amazon.com/exec/obidos/ASIN/B0006S01EQ/icongroupinterna
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Journey from Cognition to Brain to Gene: Perspectives from Williams Syndrome Ursula Bellugi and Marie I. St. George (2001); ISBN: 0262523124; http://www.amazon.com/exec/obidos/ASIN/0262523124/icongroupinterna
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Language Availabilities in Williams Syndrome (Neurocognitive Developments and Impairments) Agnes Lukacs (2005); ISBN: 9630582392; http://www.amazon.com/exec/obidos/ASIN/9630582392/icongroupinterna
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Lexical skills in Williams Syndrome: a cognitive neuropsychological analysis C.M. Temple, M. Almazan, and S. Sherwood (2002); ISBN: B000MDFDAC; http://www.amazon.com/exec/obidos/ASIN/B000MDFDAC/icongroupinterna
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Object recognition with severe spatial deficits in Williams syndrome: sparing and breakdown B. Landau, J.E. Hoffman, and N. Kurz (2006); ISBN: B000H1QWPE; http://www.amazon.com/exec/obidos/ASIN/B000H1QWPE/icongroupinterna
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Perceptual grouping ability in Williams syndrome: evidence for deviant patterns of performance E.K. Farran (2005); ISBN: B000M7F4MA; http://www.amazon.com/exec/obidos/ASIN/B000M7F4MA/icongroupinterna
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Self concept in people with Williams syndrome and Prader-Willi syndrome D. PlesaSkwerer, K. Sullivan, K. Joffre, and H. Tager-Flusberg; ISBN: B000M7WAS6; http://www.amazon.com/exec/obidos/ASIN/B000M7WAS6/icongroupinterna
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Spatial breakdown in spatial construction: Evidence from eye fixations in children with Williams syndrome J.E. Hoffman, B. Landau, and B. Pagani; ISBN: B000MEWZ5C; http://www.amazon.com/exec/obidos/ASIN/B000MEWZ5C/icongroupinterna
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Speech timing and verbal short-term memory: Evidence for contrasting deficits in Down syndrome and Williams syndrome C. Jarrold, N. Cowan, A.K. Hewes, and D.M. Ri (2004); ISBN: B000M5M7KY; http://www.amazon.com/exec/obidos/ASIN/B000M5M7KY/icongroupinterna
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Texture segmentation in Williams syndrome E.K. Farran and K. Wilmut (2007); ISBN: B000N6SD1Y; http://www.amazon.com/exec/obidos/ASIN/B000N6SD1Y/icongroupinterna
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The Official Parent's Sourcebook on Williams Syndrome: A Revised and Updated Directory for the Internet Age Icon Health Publications (2002); ISBN: 0597831238; http://www.amazon.com/exec/obidos/ASIN/0597831238/icongroupinterna
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Therapy methods and approaches used with children and adolescents with Williams syndrome, a survey Shawna Hill (2001); ISBN: B0006RYB2U; http://www.amazon.com/exec/obidos/ASIN/B0006RYB2U/icongroupinterna
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Understanding Williams Syndrome: Behavioral Patterns and Interventions Eleanor Semel and Sue R. Rosner (2003); ISBN: 0805826181; http://www.amazon.com/exec/obidos/ASIN/0805826181/icongroupinterna
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Visual search deficits in Williams-Beuren syndrome I. Montfoort, M.A. Frens, I.Th.C. Hooge, and G.C.L.v. Haselen (2007); ISBN: B000N6SCYM; http://www.amazon.com/exec/obidos/ASIN/B000N6SCYM/icongroupinterna
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Williams Syndrome - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References ICON Health Publications (2004); ISBN: 0597846863; http://www.amazon.com/exec/obidos/ASIN/0597846863/icongroupinterna
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Williams Syndrome Across Languages (Language Acquisition and Language Disorders) Susanne Bartke and Julia Siegmuller (2004); ISBN: 1588114945; http://www.amazon.com/exec/obidos/ASIN/1588114945/icongroupinterna
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Williams syndrome and specific language impairment do not support claims for developmental double dissociations and innate modularity V. Stojanovik, M. Perkins, and S. Howard; ISBN: B000M7X4B8; http://www.amazon.com/exec/obidos/ASIN/B000M7X4B8/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select LocatorPlus. Once you are in the search area, simply type Williams syndrome (or synonyms) into the search box, and select the Quick Limit Option for Keyword, Title, or Journal Title Search: Books. From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine13: •
Journey from cognition to brain to gene: perspectives from Williams Syndrome Author: Bellugi, Ursula,; Year: 2001; Cambridge, Mass.: MIT Press, c2001; ISBN: 9780262523 http://www.amazon.com/exec/obidos/ASIN/9780262523/icongroupinterna
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Williams syndrome across languages Author: Bartke, Susanne.; Year: 2004; Amsterdam; Philadelphia: John Benjamins Pub., c2004; ISBN: 9781588114 http://www.amazon.com/exec/obidos/ASIN/9781588114/icongroupinterna
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In addition to LocatorPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a Books button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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CHAPTER 4. MULTIMEDIA ON WILLIAMS SYNDROME Overview In this chapter, we show you how to find bibliographic information related to multimedia sources of information on Williams syndrome.
Bibliography: Multimedia on Williams Syndrome The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select LocatorPlus. Once you are in the search area, simply type Williams syndrome (or synonyms) into the search box, and select the Quick Limit Option for Keyword, Title, or Journal Title Search: Audiovisuals and Computer Files. From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on Williams syndrome: •
Don’t be shy, Mr. Sacks [videorecording]: Williams syndrome Source: a presentation of Films for the Humanities & Sciences; BBC; Year: 1998; Format: Videorecording; Princeton, N.J.: Films for the Humanities & Sciences, c1998
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APPENDIX A. HELP ME UNDERSTAND GENETICS Overview This appendix presents basic information about genetics in clear language and provides links to online resources.14
The Basics: Genes and How They Work This section gives you information on the basics of cells, DNA, genes, chromosomes, and proteins. What Is a Cell? Cells are the basic building blocks of all living things. The human body is composed of trillions of cells. They provide structure for the body, take in nutrients from food, convert those nutrients into energy, and carry out specialized functions. Cells also contain the body’s hereditary material and can make copies of themselves. Cells have many parts, each with a different function. Some of these parts, called organelles, are specialized structures that perform certain tasks within the cell. Human cells contain the following major parts, listed in alphabetical order: •
Cytoplasm: The cytoplasm is fluid inside the cell that surrounds the organelles.
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Endoplasmic reticulum (ER): This organelle helps process molecules created by the cell and transport them to their specific destinations either inside or outside the cell.
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Golgi apparatus: The golgi apparatus packages molecules processed by the endoplasmic reticulum to be transported out of the cell.
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Lysosomes and peroxisomes: These organelles are the recycling center of the cell. They digest foreign bacteria that invade the cell, rid the cell of toxic substances, and recycle worn-out cell components.
14 This appendix is an excerpt from the National Library of Medicine’s handbook, Help Me Understand Genetics. For the full text of the Help Me Understand Genetics handbook, see http://ghr.nlm.nih.gov/handbook.
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Mitochondria: Mitochondria are complex organelles that convert energy from food into a form that the cell can use. They have their own genetic material, separate from the DNA in the nucleus, and can make copies of themselves.
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Nucleus: The nucleus serves as the cell’s command center, sending directions to the cell to grow, mature, divide, or die. It also houses DNA (deoxyribonucleic acid), the cell’s hereditary material. The nucleus is surrounded by a membrane called the nuclear envelope, which protects the DNA and separates the nucleus from the rest of the cell.
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Plasma membrane: The plasma membrane is the outer lining of the cell. It separates the cell from its environment and allows materials to enter and leave the cell.
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Ribosomes: Ribosomes are organelles that process the cell’s genetic instructions to create proteins. These organelles can float freely in the cytoplasm or be connected to the endoplasmic reticulum. What Is DNA?
DNA, or deoxyribonucleic acid, is the hereditary material in humans and almost all other organisms. Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA). The information in DNA is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Human DNA consists of about 3 billion bases, and more than 99 percent of those bases are the same in all people. The order, or sequence, of these bases determines the information available for building and maintaining an organism, similar to the way in which letters of the alphabet appear in a certain order to form words and sentences. DNA bases pair up with each other, A with T and C with G, to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule. Together, a base, sugar, and phosphate are called a nucleotide. Nucleotides are arranged in two long strands that form a spiral called a double helix. The structure of the double helix is somewhat like a ladder, with the base pairs forming the ladder’s rungs and the sugar and phosphate molecules forming the vertical sidepieces of the ladder. An important property of DNA is that it can replicate, or make copies of itself. Each strand of DNA in the double helix can serve as a pattern for duplicating the sequence of bases. This is critical when cells divide because each new cell needs to have an exact copy of the DNA present in the old cell.
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DNA is a double helix formed by base pairs attached to a sugar-phosphate backbone. What Is Mitochondrial DNA? Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA. This genetic material is known as mitochondrial DNA or mtDNA. Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Each cell contains hundreds to thousands of mitochondria, which are located in the fluid that surrounds the nucleus (the cytoplasm). Mitochondria produce energy through a process called oxidative phosphorylation. This process uses oxygen and simple sugars to create adenosine triphosphate (ATP), the cell’s main energy source. A set of enzyme complexes, designated as complexes I-V, carry out oxidative phosphorylation within mitochondria. In addition to energy production, mitochondria play a role in several other cellular activities. For example, mitochondria help regulate the self-destruction of cells (apoptosis). They are also necessary for the production of substances such as cholesterol and heme (a component of hemoglobin, the molecule that carries oxygen in the blood). Mitochondrial DNA contains 37 genes, all of which are essential for normal mitochondrial function. Thirteen of these genes provide instructions for making enzymes involved in oxidative phosphorylation. The remaining genes provide instructions for making molecules called transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), which are chemical cousins of
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DNA. These types of RNA help assemble protein building blocks (amino acids) into functioning proteins. What Is a Gene? A gene is the basic physical and functional unit of heredity. Genes, which are made up of DNA, act as instructions to make molecules called proteins. In humans, genes vary in size from a few hundred DNA bases to more than 2 million bases. The Human Genome Project has estimated that humans have between 20,000 and 25,000 genes. Every person has two copies of each gene, one inherited from each parent. Most genes are the same in all people, but a small number of genes (less than 1 percent of the total) are slightly different between people. Alleles are forms of the same gene with small differences in their sequence of DNA bases. These small differences contribute to each person’s unique physical features.
Genes are made up of DNA. Each chromosome contains many genes. What Is a Chromosome? In the nucleus of each cell, the DNA molecule is packaged into thread-like structures called chromosomes. Each chromosome is made up of DNA tightly coiled many times around proteins called histones that support its structure. Chromosomes are not visible in the cell’s nucleus—not even under a microscope—when the cell is not dividing. However, the DNA that makes up chromosomes becomes more tightly packed during cell division and is then visible under a microscope. Most of what researchers know about chromosomes was learned by observing chromosomes during cell division. Each chromosome has a constriction point called the centromere, which divides the chromosome into two sections, or “arms.” The short arm of the chromosome is labeled the “p arm.” The long arm of the chromosome is labeled the “q arm.” The location of the centromere on each chromosome gives the chromosome its characteristic shape, and can be used to help describe the location of specific genes.
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DNA and histone proteins are packaged into structures called chromosomes. How Many Chromosomes Do People Have? In humans, each cell normally contains 23 pairs of chromosomes, for a total of 46. Twentytwo of these pairs, called autosomes, look the same in both males and females. The 23rd pair, the sex chromosomes, differ between males and females. Females have two copies of the X chromosome, while males have one X and one Y chromosome.
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The 22 autosomes are numbered by size. The other two chromosomes, X and Y, are the sex chromosomes. This picture of the human chromosomes lined up in pairs is called a karyotype. How Do Geneticists Indicate the Location of a Gene? Geneticists use maps to describe the location of a particular gene on a chromosome. One type of map uses the cytogenetic location to describe a gene’s position. The cytogenetic location is based on a distinctive pattern of bands created when chromosomes are stained with certain chemicals. Another type of map uses the molecular location, a precise description of a gene’s position on a chromosome. The molecular location is based on the sequence of DNA building blocks (base pairs) that make up the chromosome. Cytogenetic Location Geneticists use a standardized way of describing a gene’s cytogenetic location. In most cases, the location describes the position of a particular band on a stained chromosome: 17q12 It can also be written as a range of bands, if less is known about the exact location: 17q12-q21 The combination of numbers and letters provide a gene’s “address” on a chromosome. This address is made up of several parts: •
The chromosome on which the gene can be found. The first number or letter used to describe a gene’s location represents the chromosome. Chromosomes 1 through 22 (the autosomes) are designated by their chromosome number. The sex chromosomes are designated by X or Y.
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•
The arm of the chromosome. Each chromosome is divided into two sections (arms) based on the location of a narrowing (constriction) called the centromere. By convention, the shorter arm is called p, and the longer arm is called q. The chromosome arm is the second part of the gene’s address. For example, 5q is the long arm of chromosome 5, and Xp is the short arm of the X chromosome.
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The position of the gene on the p or q arm. The position of a gene is based on a distinctive pattern of light and dark bands that appear when the chromosome is stained in a certain way. The position is usually designated by two digits (representing a region and a band), which are sometimes followed by a decimal point and one or more additional digits (representing sub-bands within a light or dark area). The number indicating the gene position increases with distance from the centromere. For example: 14q21 represents position 21 on the long arm of chromosome 14. 14q21 is closer to the centromere than 14q22.
Sometimes, the abbreviations “cen” or “ter” are also used to describe a gene’s cytogenetic location. “Cen” indicates that the gene is very close to the centromere. For example, 16pcen refers to the short arm of chromosome 16 near the centromere. “Ter” stands for terminus, which indicates that the gene is very close to the end of the p or q arm. For example, 14qter refers to the tip of the long arm of chromosome 14. (“Tel” is also sometimes used to describe a gene’s location. “Tel” stands for telomeres, which are at the ends of each chromosome. The abbreviations “tel” and “ter” refer to the same location.)
The CFTR gene is located on the long arm of chromosome 7 at position 7q31.2.
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Molecular Location The Human Genome Project, an international research effort completed in 2003, determined the sequence of base pairs for each human chromosome. This sequence information allows researchers to provide a more specific address than the cytogenetic location for many genes. A gene’s molecular address pinpoints the location of that gene in terms of base pairs. For example, the molecular location of the APOE gene on chromosome 19 begins with base pair 50,100,901 and ends with base pair 50,104,488. This range describes the gene’s precise position on chromosome 19 and indicates the size of the gene (3,588 base pairs). Knowing a gene’s molecular location also allows researchers to determine exactly how far the gene is from other genes on the same chromosome. Different groups of researchers often present slightly different values for a gene’s molecular location. Researchers interpret the sequence of the human genome using a variety of methods, which can result in small differences in a gene’s molecular address. For example, the National Center for Biotechnology Information (NCBI) identifies the molecular location of the APOE gene as base pair 50,100,901 to base pair 50,104,488 on chromosome 19. The Ensembl database identifies the location of this gene as base pair 50,100,879 to base pair 50,104,489 on chromosome 19. Neither of these addresses is incorrect; they represent different interpretations of the same data. For consistency, Genetics Home Reference presents data from NCBI for the molecular location of genes. What Are Proteins and What Do They Do? Proteins are large, complex molecules that play many critical roles in the body. They do most of the work in cells and are required for the structure, function, and regulation of the body’s tissues and organs. Proteins are made up of hundreds or thousands of smaller units called amino acids, which are attached to one another in long chains. There are 20 different types of amino acids that can be combined to make a protein. The sequence of amino acids determines each protein’s unique 3-dimensional structure and its specific function.
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Examples of Protein Functions Proteins can be described according to their large range of functions in the body, listed in alphabetical order: Function Antibody
Description Antibodies bind to specific foreign particles, such as viruses and bacteria, to help protect the body.
Example Immunoglobulin G (IgG)
Enzyme
Enzymes carry out almost all of the thousands of chemical reactions that take place in cells. They also assist with the formation of new molecules by reading the genetic information stored in DNA.
Phenylalanine hydroxylase
Messenger
Messenger proteins, such as some types of hormones, transmit signals to coordinate biological processes between different cells, tissues, and organs.
Growth hormone
Structural component
These proteins provide structure and support for cells. On a larger scale, they also allow the body to move. These proteins bind and carry atoms and small molecules within cells and throughout the body.
Actin
Transport/storage
Ferritin
How Does a Gene Make a Protein? Most genes contain the information needed to make functional molecules called proteins. (A few genes produce other molecules that help the cell assemble proteins.) The journey from gene to protein is complex and tightly controlled within each cell. It consists of two major steps: transcription and translation. Together, transcription and translation are known as gene expression. During the process of transcription, the information stored in a gene’s DNA is transferred to a similar molecule called RNA (ribonucleic acid) in the cell nucleus. Both RNA and DNA are made up of a chain of nucleotide bases, but they have slightly different chemical properties. The type of RNA that contains the information for making a protein is called messenger RNA (mRNA) because it carries the information, or message, from the DNA out of the nucleus into the cytoplasm. Translation, the second step in getting from a gene to a protein, takes place in the cytoplasm. The mRNA interacts with a specialized complex called a ribosome, which “reads” the sequence of mRNA bases. Each sequence of three bases, called a codon, usually codes for
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one particular amino acid. (Amino acids are the building blocks of proteins.) A type of RNA called transfer RNA (tRNA) assembles the protein, one amino acid at a time. Protein assembly continues until the ribosome encounters a “stop” codon (a sequence of three bases that does not code for an amino acid). The flow of information from DNA to RNA to proteins is one of the fundamental principles of molecular biology. It is so important that it is sometimes called the “central dogma.”
Through the processes of transcription and translation, information from genes is used to make proteins.
Can Genes Be Turned On and Off in Cells? Each cell expresses, or turns on, only a fraction of its genes. The rest of the genes are repressed, or turned off. The process of turning genes on and off is known as gene regulation. Gene regulation is an important part of normal development. Genes are turned on and off in different patterns during development to make a brain cell look and act different from a liver cell or a muscle cell, for example. Gene regulation also allows cells to react quickly to changes in their environments. Although we know that the regulation of genes is critical for life, this complex process is not yet fully understood. Gene regulation can occur at any point during gene expression, but most commonly occurs at the level of transcription (when the information in a gene’s DNA is transferred to mRNA). Signals from the environment or from other cells activate proteins called transcription factors. These proteins bind to regulatory regions of a gene and increase or decrease the level of transcription. By controlling the level of transcription, this process can determine the amount of protein product that is made by a gene at any given time.
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How Do Cells Divide? There are two types of cell division: mitosis and meiosis. Most of the time when people refer to “cell division,” they mean mitosis, the process of making new body cells. Meiosis is the type of cell division that creates egg and sperm cells. Mitosis is a fundamental process for life. During mitosis, a cell duplicates all of its contents, including its chromosomes, and splits to form two identical daughter cells. Because this process is so critical, the steps of mitosis are carefully controlled by a number of genes. When mitosis is not regulated correctly, health problems such as cancer can result. The other type of cell division, meiosis, ensures that humans have the same number of chromosomes in each generation. It is a two-step process that reduces the chromosome number by half—from 46 to 23—to form sperm and egg cells. When the sperm and egg cells unite at conception, each contributes 23 chromosomes so the resulting embryo will have the usual 46. Meiosis also allows genetic variation through a process of DNA shuffling while the cells are dividing.
Mitosis and meiosis, the two types of cell division. How Do Genes Control the Growth and Division of Cells? A variety of genes are involved in the control of cell growth and division. The cell cycle is the cell’s way of replicating itself in an organized, step-by-step fashion. Tight regulation of this process ensures that a dividing cell’s DNA is copied properly, any errors in the DNA are repaired, and each daughter cell receives a full set of chromosomes. The cycle has checkpoints (also called restriction points), which allow certain genes to check for mistakes and halt the cycle for repairs if something goes wrong.
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If a cell has an error in its DNA that cannot be repaired, it may undergo programmed cell death (apoptosis). Apoptosis is a common process throughout life that helps the body get rid of cells it doesn’t need. Cells that undergo apoptosis break apart and are recycled by a type of white blood cell called a macrophage. Apoptosis protects the body by removing genetically damaged cells that could lead to cancer, and it plays an important role in the development of the embryo and the maintenance of adult tissues. Cancer results from a disruption of the normal regulation of the cell cycle. When the cycle proceeds without control, cells can divide without order and accumulate genetic defects that can lead to a cancerous tumor.
Genetic Mutations and Health This section presents basic information about gene mutations, chromosomal changes, and conditions that run in families.15 What Is a Gene Mutation and How Do Mutations Occur? A gene mutation is a permanent change in the DNA sequence that makes up a gene. Mutations range in size from a single DNA building block (DNA base) to a large segment of a chromosome. Gene mutations occur in two ways: they can be inherited from a parent or acquired during a person’s lifetime. Mutations that are passed from parent to child are called hereditary mutations or germline mutations (because they are present in the egg and sperm cells, which are also called germ cells). This type of mutation is present throughout a person’s life in virtually every cell in the body. Mutations that occur only in an egg or sperm cell, or those that occur just after fertilization, are called new (de novo) mutations. De novo mutations may explain genetic disorders in which an affected child has a mutation in every cell, but has no family history of the disorder. Acquired (or somatic) mutations occur in the DNA of individual cells at some time during a person’s life. These changes can be caused by environmental factors such as ultraviolet radiation from the sun, or can occur if a mistake is made as DNA copies itself during cell division. Acquired mutations in somatic cells (cells other than sperm and egg cells) cannot be passed on to the next generation. Mutations may also occur in a single cell within an early embryo. As all the cells divide during growth and development, the individual will have some cells with the mutation and some cells without the genetic change. This situation is called mosaicism. Some genetic changes are very rare; others are common in the population. Genetic changes that occur in more than 1 percent of the population are called polymorphisms. They are common enough to be considered a normal variation in the DNA. Polymorphisms are 15
This section has been adapted from the National Library of Medicine’s handbook, Help Me Understand Genetics, which presents basic information about genetics in clear language and provides links to online resources: http://ghr.nlm.nih.gov/handbook.
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responsible for many of the normal differences between people such as eye color, hair color, and blood type. Although many polymorphisms have no negative effects on a person’s health, some of these variations may influence the risk of developing certain disorders. How Can Gene Mutations Affect Health and Development? To function correctly, each cell depends on thousands of proteins to do their jobs in the right places at the right times. Sometimes, gene mutations prevent one or more of these proteins from working properly. By changing a gene’s instructions for making a protein, a mutation can cause the protein to malfunction or to be missing entirely. When a mutation alters a protein that plays a critical role in the body, it can disrupt normal development or cause a medical condition. A condition caused by mutations in one or more genes is called a genetic disorder. In some cases, gene mutations are so severe that they prevent an embryo from surviving until birth. These changes occur in genes that are essential for development, and often disrupt the development of an embryo in its earliest stages. Because these mutations have very serious effects, they are incompatible with life. It is important to note that genes themselves do not cause disease—genetic disorders are caused by mutations that make a gene function improperly. For example, when people say that someone has “the cystic fibrosis gene,” they are usually referring to a mutated version of the CFTR gene, which causes the disease. All people, including those without cystic fibrosis, have a version of the CFTR gene. Do All Gene Mutations Affect Health and Development? No, only a small percentage of mutations cause genetic disorders—most have no impact on health or development. For example, some mutations alter a gene’s DNA base sequence but do not change the function of the protein made by the gene. Often, gene mutations that could cause a genetic disorder are repaired by certain enzymes before the gene is expressed (makes a protein). Each cell has a number of pathways through which enzymes recognize and repair mistakes in DNA. Because DNA can be damaged or mutated in many ways, DNA repair is an important process by which the body protects itself from disease. A very small percentage of all mutations actually have a positive effect. These mutations lead to new versions of proteins that help an organism and its future generations better adapt to changes in their environment. For example, a beneficial mutation could result in a protein that protects the organism from a new strain of bacteria. For More Information about DNA Repair and the Health Effects of Gene Mutations •
The University of Utah Genetic Science Learning Center provides information about genetic disorders that explains why some mutations cause disorders but others do not. (Refer to the questions in the far right column.) See http://learn.genetics.utah.edu/units/disorders/whataregd/.
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Additional information about DNA repair is available from the NCBI Science Primer. In the chapter called “What Is A Cell?”, scroll down to the heading “DNA Repair Mechanisms.” See http://www.ncbi.nlm.nih.gov/About/primer/genetics_cell.html. What Kinds of Gene Mutations Are Possible?
The DNA sequence of a gene can be altered in a number of ways. Gene mutations have varying effects on health, depending on where they occur and whether they alter the function of essential proteins. The types of mutations include: •
Missense mutation: This type of mutation is a change in one DNA base pair that results in the substitution of one amino acid for another in the protein made by a gene.
•
Nonsense mutation: A nonsense mutation is also a change in one DNA base pair. Instead of substituting one amino acid for another, however, the altered DNA sequence prematurely signals the cell to stop building a protein. This type of mutation results in a shortened protein that may function improperly or not at all.
•
Insertion: An insertion changes the number of DNA bases in a gene by adding a piece of DNA. As a result, the protein made by the gene may not function properly.
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Deletion: A deletion changes the number of DNA bases by removing a piece of DNA. Small deletions may remove one or a few base pairs within a gene, while larger deletions can remove an entire gene or several neighboring genes. The deleted DNA may alter the function of the resulting protein(s).
•
Duplication: A duplication consists of a piece of DNA that is abnormally copied one or more times. This type of mutation may alter the function of the resulting protein.
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Frameshift mutation: This type of mutation occurs when the addition or loss of DNA bases changes a gene’s reading frame. A reading frame consists of groups of 3 bases that each code for one amino acid. A frameshift mutation shifts the grouping of these bases and changes the code for amino acids. The resulting protein is usually nonfunctional. Insertions, deletions, and duplications can all be frameshift mutations.
•
Repeat expansion: Nucleotide repeats are short DNA sequences that are repeated a number of times in a row. For example, a trinucleotide repeat is made up of 3-base-pair sequences, and a tetranucleotide repeat is made up of 4-base-pair sequences. A repeat expansion is a mutation that increases the number of times that the short DNA sequence is repeated. This type of mutation can cause the resulting protein to function improperly. Can Changes in Chromosomes Affect Health and Development?
Changes that affect entire chromosomes or segments of chromosomes can cause problems with growth, development, and function of the body’s systems. These changes can affect many genes along the chromosome and alter the proteins made by those genes. Conditions caused by a change in the number or structure of chromosomes are known as chromosomal disorders. Human cells normally contain 23 pairs of chromosomes, for a total of 46 chromosomes in each cell. A change in the number of chromosomes leads to a chromosomal disorder. These changes can occur during the formation of reproductive cells (eggs and sperm) or in early fetal development. A gain or loss of chromosomes from the normal 46 is called aneuploidy.
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The most common form of aneuploidy is trisomy, or the presence of an extra chromosome in each cell. “Tri-” is Greek for “three”; people with trisomy have three copies of a particular chromosome in each cell instead of the normal two copies. Down syndrome is an example of a condition caused by trisomy—people with Down syndrome typically have three copies of chromosome 21 in each cell, for a total of 47 chromosomes per cell. Monosomy, or the loss of one chromosome from each cell, is another kind of aneuploidy. “Mono-” is Greek for “one”; people with monosomy have one copy of a particular chromosome in each cell instead of the normal two copies. Turner syndrome is a condition caused by monosomy. Women with Turner syndrome are often missing one copy of the X chromosome in every cell, for a total of 45 chromosomes per cell. Chromosomal disorders can also be caused by changes in chromosome structure. These changes are caused by the breakage and reunion of chromosome segments when an egg or sperm cell is formed or in early fetal development. Pieces of DNA can be rearranged within one chromosome, or transferred between two or more chromosomes. The effects of structural changes depend on their size and location. Many different structural changes are possible; some cause medical problems, while others may have no effect on a person’s health. Many cancer cells also have changes in their chromosome number or structure. These changes most often occur in somatic cells (cells other than eggs and sperm) during a person’s lifetime. Can Changes in Mitochondrial DNA Affect Health and Development? Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA (known as mitochondrial DNA or mtDNA). In some cases, inherited changes in mitochondrial DNA can cause problems with growth, development, and function of the body’s systems. These mutations disrupt the mitochondria’s ability to generate energy efficiently for the cell. Conditions caused by mutations in mitochondrial DNA often involve multiple organ systems. The effects of these conditions are most pronounced in organs and tissues that require a lot of energy (such as the heart, brain, and muscles). Although the health consequences of inherited mitochondrial DNA mutations vary widely, frequently observed features include muscle weakness and wasting, problems with movement, diabetes, kidney failure, heart disease, loss of intellectual functions (dementia), hearing loss, and abnormalities involving the eyes and vision. Mitochondrial DNA is also prone to noninherited (somatic) mutations. Somatic mutations occur in the DNA of certain cells during a person’s lifetime, and typically are not passed to future generations. Because mitochondrial DNA has a limited ability to repair itself when it is damaged, these mutations tend to build up over time. A buildup of somatic mutations in mitochondrial DNA has been associated with some forms of cancer and an increased risk of certain age-related disorders such as heart disease, Alzheimer disease, and Parkinson disease. Additionally, research suggests that the progressive accumulation of these mutations over a person’s lifetime may play a role in the normal process of aging.
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What Are Complex or Multifactorial Disorders? Researchers are learning that nearly all conditions and diseases have a genetic component. Some disorders, such as sickle cell anemia and cystic fibrosis, are caused by mutations in a single gene. The causes of many other disorders, however, are much more complex. Common medical problems such as heart disease, diabetes, and obesity do not have a single genetic cause—they are likely associated with the effects of multiple genes in combination with lifestyle and environmental factors. Conditions caused by many contributing factors are called complex or multifactorial disorders. Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance. This makes it difficult to determine a person’s risk of inheriting or passing on these disorders. Complex disorders are also difficult to study and treat because the specific factors that cause most of these disorders have not yet been identified. By 2010, however, researchers predict they will have found the major contributing genes for many common complex disorders. What Information about a Genetic Condition Can Statistics Provide? Statistical data can provide general information about how common a condition is, how many people have the condition, or how likely it is that a person will develop the condition. Statistics are not personalized, however—they offer estimates based on groups of people. By taking into account a person’s family history, medical history, and other factors, a genetics professional can help interpret what statistics mean for a particular patient. Common Statistical Terms Some statistical terms are commonly used when describing genetic conditions and other disorders. These terms include: Statistical Term Incidence
Description The incidence of a gene mutation or a genetic disorder is the number of people who are born with the mutation or disorder in a specified group per year. Incidence is often written in the form “1 in [a number]” or as a total number of live births.
Examples About 1 in 200,000 people in the United States are born with syndrome A each year. An estimated 15,000 infants with syndrome B were born last year worldwide.
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Prevalence
The prevalence of a gene mutation or a genetic disorder is the total number of people in a specified group at a given time who have the mutation or disorder. This term includes both newly diagnosed and preexisting cases in people of any age. Prevalence is often written in the form “1 in [a number]” or as a total number of people who have a condition.
Approximately 1 in 100,000 people in the United States have syndrome A at the present time. About 100,000 children worldwide currently have syndrome B.
Mortality
Mortality is the number of deaths from a particular disorder occurring in a specified group per year. Mortality is usually expressed as a total number of deaths.
An estimated 12,000 people worldwide died from syndrome C in 2002.
Lifetime risk
Lifetime risk is the average risk of developing a particular disorder at some point during a lifetime. Lifetime risk is often written as a percentage or as “1 in [a number].” It is important to remember that the risk per year or per decade is much lower than the lifetime risk. In addition, other factors may increase or decrease a person’s risk as compared with the average.
Approximately 1 percent of people in the United States develop disorder D during their lifetimes. The lifetime risk of developing disorder D is 1 in 100.
Naming Genetic Conditions Genetic conditions are not named in one standard way (unlike genes, which are given an official name and symbol by a formal committee). Doctors who treat families with a particular disorder are often the first to propose a name for the condition. Expert working groups may later revise the name to improve its usefulness. Naming is important because it allows accurate and effective communication about particular conditions, which will ultimately help researchers find new approaches to treatment. Disorder names are often derived from one or a combination of sources: •
The basic genetic or biochemical defect that causes the condition (for example, alpha-1 antitrypsin deficiency)
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One or more major signs or symptoms of the disorder (for example, sickle cell anemia)
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The parts of the body affected by the condition (for example, retinoblastoma)
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The name of a physician or researcher, often the first person to describe the disorder (for example, Marfan syndrome, which was named after Dr. Antoine Bernard-Jean Marfan)
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A geographic area (for example, familial Mediterranean fever, which occurs mainly in populations bordering the Mediterranean Sea)
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The name of a patient or family with the condition (for example, amyotrophic lateral sclerosis, which is also called Lou Gehrig disease after a famous baseball player who had the condition).
Disorders named after a specific person or place are called eponyms. There is debate as to whether the possessive form (e.g., Alzheimer’s disease) or the nonpossessive form (Alzheimer disease) of eponyms is preferred. As a rule, medical geneticists use the nonpossessive form, and this form may become the standard for doctors in all fields of medicine. Genetics Home Reference uses the nonpossessive form of eponyms. Genetics Home Reference consults with experts in the field of medical genetics to provide the current, most accurate name for each disorder. Alternate names are included as synonyms. Naming genes The HUGO Gene Nomenclature Committee (HGNC) designates an official name and symbol (an abbreviation of the name) for each known human gene. Some official gene names include additional information in parentheses, such as related genetic conditions, subtypes of a condition, or inheritance pattern. The HGNC is a non-profit organization funded by the U.K. Medical Research Council and the U.S. National Institutes of Health. The Committee has named more than 13,000 of the estimated 20,000 to 25,000 genes in the human genome. During the research process, genes often acquire several alternate names and symbols. Different researchers investigating the same gene may each give the gene a different name, which can cause confusion. The HGNC assigns a unique name and symbol to each human gene, which allows effective organization of genes in large databanks, aiding the advancement of research. For specific information about how genes are named, refer to the HGNC’s Guidelines for Human Gene Nomenclature. Genetics Home Reference describes genes using the HGNC’s official gene names and gene symbols. Genetics Home Reference frequently presents the symbol and name separated with a colon (for example, FGFR4: Fibroblast growth factor receptor 4).
Inheriting Genetic Conditions This section gives you information on inheritance patterns and understanding risk. What Does It Mean If a Disorder Seems to Run in My Family? A particular disorder might be described as “running in a family” if more than one person in the family has the condition. Some disorders that affect multiple family members are caused by gene mutations, which can be inherited (passed down from parent to child). Other conditions that appear to run in families are not inherited. Instead, environmental factors
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such as dietary habits or a combination of genetic and environmental factors are responsible for these disorders. It is not always easy to determine whether a condition in a family is inherited. A genetics professional can use a person’s family history (a record of health information about a person’s immediate and extended family) to help determine whether a disorder has a genetic component.
Some disorders are seen in more than one generation of a family. Why Is It Important to Know My Family Medical History? A family medical history is a record of health information about a person and his or her close relatives. A complete record includes information from three generations of relatives,
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including children, brothers and sisters, parents, aunts and uncles, nieces and nephews, grandparents, and cousins. Families have many factors in common, including their genes, environment, and lifestyle. Together, these factors can give clues to medical conditions that may run in a family. By noticing patterns of disorders among relatives, healthcare professionals can determine whether an individual, other family members, or future generations may be at an increased risk of developing a particular condition. A family medical history can identify people with a higher-than-usual chance of having common disorders, such as heart disease, high blood pressure, stroke, certain cancers, and diabetes. These complex disorders are influenced by a combination of genetic factors, environmental conditions, and lifestyle choices. A family history also can provide information about the risk of rarer conditions caused by mutations in a single gene, such as cystic fibrosis and sickle cell anemia. While a family medical history provides information about the risk of specific health concerns, having relatives with a medical condition does not mean that an individual will definitely develop that condition. On the other hand, a person with no family history of a disorder may still be at risk of developing that disorder. Knowing one’s family medical history allows a person to take steps to reduce his or her risk. For people at an increased risk of certain cancers, healthcare professionals may recommend more frequent screening (such as mammography or colonoscopy) starting at an earlier age. Healthcare providers may also encourage regular checkups or testing for people with a medical condition that runs in their family. Additionally, lifestyle changes such as adopting a healthier diet, getting regular exercise, and quitting smoking help many people lower their chances of developing heart disease and other common illnesses. The easiest way to get information about family medical history is to talk to relatives about their health. Have they had any medical problems, and when did they occur? A family gathering could be a good time to discuss these issues. Additionally, obtaining medical records and other documents (such as obituaries and death certificates) can help complete a family medical history. It is important to keep this information up-to-date and to share it with a healthcare professional regularly. What Are the Different Ways in which a Genetic Condition Can Be Inherited? Some genetic conditions are caused by mutations in a single gene. These conditions are usually inherited in one of several straightforward patterns, depending on the gene involved: Inheritance Pattern Autosomal dominant
Description One mutated copy of the gene in each cell is sufficient for a person to be affected by an autosomal dominant disorder. Each affected person usually has one affected parent. Autosomal dominant disorders tend to occur in every generation of an affected family.
Examples Huntington disease, neurofibromatosis type 1
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Autosomal recessive
Two mutated copies of the gene are present in each cell when a person has an autosomal recessive disorder. An affected person usually has unaffected parents who each carry a single copy of the mutated gene (and are referred to as carriers). Autosomal recessive disorders are typically not seen in every generation of an affected family.
cystic fibrosis, sickle cell anemia
X-linked dominant
X-linked dominant disorders are caused by mutations in genes on the X chromosome. Females are more frequently affected than males, and the chance of passing on an X-linked dominant disorder differs between men and women. Families with an X-linked dominant disorder often have both affected males and affected females in each generation. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons (no male-to-male transmission).
fragile X syndrome
X-linked recessive
X-linked recessive disorders are also caused by mutations in genes on the X chromosome. Males are more frequently affected than females, and the chance of passing on the disorder differs between men and women. Families with an X-linked recessive disorder often have affected males, but rarely affected females, in each generation. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons (no male-to-male transmission).
hemophilia, Fabry disease
Codominant
In codominant inheritance, two different versions (alleles) of a gene can be expressed, and each version makes a slightly different protein. Both alleles influence the genetic trait or determine the characteristics of the genetic condition.
ABO blood group, alpha-1 antitrypsin deficiency
Mitochondrial
This type of inheritance, also known as maternal inheritance, applies to genes in mitochondrial DNA. Mitochondria, which are structures in each cell that convert molecules into energy, each contain a small amount of DNA. Because only egg cells contribute mitochondria to the developing embryo, only females can pass on mitochondrial conditions to their children. Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children.
Leber hereditary optic neuropathy (LHON)
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Many other disorders are caused by a combination of the effects of multiple genes or by interactions between genes and the environment. Such disorders are more difficult to analyze because their genetic causes are often unclear, and they do not follow the patterns of inheritance described above. Examples of conditions caused by multiple genes or gene/environment interactions include heart disease, diabetes, schizophrenia, and certain types of cancer. Disorders caused by changes in the number or structure of chromosomes do not follow the straightforward patterns of inheritance listed above. Other genetic factors can also influence how a disorder is inherited. If a Genetic Disorder Runs in My Family, What Are the Chances That My Children Will Have the Condition? When a genetic disorder is diagnosed in a family, family members often want to know the likelihood that they or their children will develop the condition. This can be difficult to predict in some cases because many factors influence a person’s chances of developing a genetic condition. One important factor is how the condition is inherited. For example: •
Autosomal dominant inheritance: A person affected by an autosomal dominant disorder has a 50 percent chance of passing the mutated gene to each child. The chance that a child will not inherit the mutated gene is also 50 percent.
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Autosomal recessive inheritance: Two unaffected people who each carry one copy of the mutated gene for an autosomal recessive disorder (carriers) have a 25 percent chance with each pregnancy of having a child affected by the disorder. The chance with each pregnancy of having an unaffected child who is a carrier of the disorder is 50 percent, and the chance that a child will not have the disorder and will not be a carrier is 25 percent.
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X-linked dominant inheritance: The chance of passing on an X-linked dominant condition differs between men and women because men have one X chromosome and one Y chromosome, while women have two X chromosomes. A man passes on his Y chromosome to all of his sons and his X chromosome to all of his daughters. Therefore, the sons of a man with an X-linked dominant disorder will not be affected, but all of his daughters will inherit the condition. A woman passes on one or the other of her X chromosomes to each child. Therefore, a woman with an X-linked dominant disorder has a 50 percent chance of having an affected daughter or son with each pregnancy.
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X-linked recessive inheritance: Because of the difference in sex chromosomes, the probability of passing on an X-linked recessive disorder also differs between men and women. The sons of a man with an X-linked recessive disorder will not be affected, and his daughters will carry one copy of the mutated gene. With each pregnancy, a woman who carries an X-linked recessive disorder has a 50 percent chance of having sons who are affected and a 50 percent chance of having daughters who carry one copy of the mutated gene.
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Codominant inheritance: In codominant inheritance, each parent contributes a different version of a particular gene, and both versions influence the resulting genetic trait. The chance of developing a genetic condition with codominant inheritance, and the characteristic features of that condition, depend on which versions of the gene are passed from parents to their child.
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Mitochondrial inheritance: Mitochondria, which are the energy-producing centers inside cells, each contain a small amount of DNA. Disorders with mitochondrial inheritance result from mutations in mitochondrial DNA. Although mitochondrial
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disorders can affect both males and females, only females can pass mutations in mitochondrial DNA to their children. A woman with a disorder caused by changes in mitochondrial DNA will pass the mutation to all of her daughters and sons, but the children of a man with such a disorder will not inherit the mutation. It is important to note that the chance of passing on a genetic condition applies equally to each pregnancy. For example, if a couple has a child with an autosomal recessive disorder, the chance of having another child with the disorder is still 25 percent (or 1 in 4). Having one child with a disorder does not “protect” future children from inheriting the condition. Conversely, having a child without the condition does not mean that future children will definitely be affected. Although the chances of inheriting a genetic condition appear straightforward, factors such as a person’s family history and the results of genetic testing can sometimes modify those chances. In addition, some people with a disease-causing mutation never develop any health problems or may experience only mild symptoms of the disorder. If a disease that runs in a family does not have a clear-cut inheritance pattern, predicting the likelihood that a person will develop the condition can be particularly difficult. Estimating the chance of developing or passing on a genetic disorder can be complex. Genetics professionals can help people understand these chances and help them make informed decisions about their health. Factors that Influence the Effects of Particular Genetic Changes Reduced penetrance and variable expressivity are factors that influence the effects of particular genetic changes. These factors usually affect disorders that have an autosomal dominant pattern of inheritance, although they are occasionally seen in disorders with an autosomal recessive inheritance pattern. Reduced Penetrance Penetrance refers to the proportion of people with a particular genetic change (such as a mutation in a specific gene) who exhibit signs and symptoms of a genetic disorder. If some people with the mutation do not develop features of the disorder, the condition is said to have reduced (or incomplete) penetrance. Reduced penetrance often occurs with familial cancer syndromes. For example, many people with a mutation in the BRCA1 or BRCA2 gene will develop cancer during their lifetime, but some people will not. Doctors cannot predict which people with these mutations will develop cancer or when the tumors will develop. Reduced penetrance probably results from a combination of genetic, environmental, and lifestyle factors, many of which are unknown. This phenomenon can make it challenging for genetics professionals to interpret a person’s family medical history and predict the risk of passing a genetic condition to future generations. Variable Expressivity Although some genetic disorders exhibit little variation, most have signs and symptoms that differ among affected individuals. Variable expressivity refers to the range of signs and
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symptoms that can occur in different people with the same genetic condition. For example, the features of Marfan syndrome vary widely— some people have only mild symptoms (such as being tall and thin with long, slender fingers), while others also experience lifethreatening complications involving the heart and blood vessels. Although the features are highly variable, most people with this disorder have a mutation in the same gene (FBN1). As with reduced penetrance, variable expressivity is probably caused by a combination of genetic, environmental, and lifestyle factors, most of which have not been identified. If a genetic condition has highly variable signs and symptoms, it may be challenging to diagnose. What Do Geneticists Mean by Anticipation? The signs and symptoms of some genetic conditions tend to become more severe and appear at an earlier age as the disorder is passed from one generation to the next. This phenomenon is called anticipation. Anticipation is most often seen with certain genetic disorders of the nervous system, such as Huntington disease, myotonic dystrophy, and fragile X syndrome. Anticipation typically occurs with disorders that are caused by an unusual type of mutation called a trinucleotide repeat expansion. A trinucleotide repeat is a sequence of three DNA building blocks (nucleotides) that is repeated a number of times in a row. DNA segments with an abnormal number of these repeats are unstable and prone to errors during cell division. The number of repeats can change as the gene is passed from parent to child. If the number of repeats increases, it is known as a trinucleotide repeat expansion. In some cases, the trinucleotide repeat may expand until the gene stops functioning normally. This expansion causes the features of some disorders to become more severe with each successive generation. Most genetic disorders have signs and symptoms that differ among affected individuals, including affected people in the same family. Not all of these differences can be explained by anticipation. A combination of genetic, environmental, and lifestyle factors is probably responsible for the variability, although many of these factors have not been identified. Researchers study multiple generations of affected family members and consider the genetic cause of a disorder before determining that it shows anticipation. What Is Genomic Imprinting? Genomic imprinting is a factor that influences how some genetic conditions are inherited. People inherit two copies of their genes—one from their mother and one from their father. Usually both copies of each gene are active, or “turned on,” in cells. In some cases, however, only one of the two copies is normally turned on. Which copy is active depends on the parent of origin: some genes are normally active only when they are inherited from a person’s father; others are active only when inherited from a person’s mother. This phenomenon is known as genomic imprinting. In genes that undergo genomic imprinting, the parent of origin is often marked, or “stamped,” on the gene during the formation of egg and sperm cells. This stamping process, called methylation, is a chemical reaction that attaches small molecules called methyl groups to certain segments of DNA. These molecules identify which copy of a gene was inherited
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from the mother and which was inherited from the father. The addition and removal of methyl groups can be used to control the activity of genes. Only a small percentage of all human genes undergo genomic imprinting. Researchers are not yet certain why some genes are imprinted and others are not. They do know that imprinted genes tend to cluster together in the same regions of chromosomes. Two major clusters of imprinted genes have been identified in humans, one on the short (p) arm of chromosome 11 (at position 11p15) and another on the long (q) arm of chromosome 15 (in the region 15q11 to 15q13). What Is Uniparental Disomy? Uniparental disomy is a factor that influences how some genetic conditions are inherited. Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent. UPD can occur as a random event during the formation of egg or sperm cells or may happen in early fetal development. In many cases, UPD likely has no effect on health or development. Because most genes are not imprinted, it doesn’t matter if a person inherits both copies from one parent instead of one copy from each parent. In some cases, however, it does make a difference whether a gene is inherited from a person’s mother or father. A person with UPD may lack any active copies of essential genes that undergo genomic imprinting. This loss of gene function can lead to delayed development, mental retardation, or other medical problems. Several genetic disorders can result from UPD or a disruption of normal genomic imprinting. The most well-known conditions include Prader-Willi syndrome, which is characterized by uncontrolled eating and obesity, and Angelman syndrome, which causes mental retardation and impaired speech. Both of these disorders can be caused by UPD or other errors in imprinting involving genes on the long arm of chromosome 15. Other conditions, such as Beckwith-Wiedemann syndrome (a disorder characterized by accelerated growth and an increased risk of cancerous tumors), are associated with abnormalities of imprinted genes on the short arm of chromosome 11. Are Chromosomal Disorders Inherited? Although it is possible to inherit some types of chromosomal abnormalities, most chromosomal disorders (such as Down syndrome and Turner syndrome) are not passed from one generation to the next. Some chromosomal conditions are caused by changes in the number of chromosomes. These changes are not inherited, but occur as random events during the formation of reproductive cells (eggs and sperm). An error in cell division called nondisjunction results in reproductive cells with an abnormal number of chromosomes. For example, a reproductive cell may accidentally gain or lose one copy of a chromosome. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra or missing chromosome in each of the body’s cells.
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Changes in chromosome structure can also cause chromosomal disorders. Some changes in chromosome structure can be inherited, while others occur as random accidents during the formation of reproductive cells or in early fetal development. Because the inheritance of these changes can be complex, people concerned about this type of chromosomal abnormality may want to talk with a genetics professional. Some cancer cells also have changes in the number or structure of their chromosomes. Because these changes occur in somatic cells (cells other than eggs and sperm), they cannot be passed from one generation to the next. Why Are Some Genetic Conditions More Common in Particular Ethnic Groups? Some genetic disorders are more likely to occur among people who trace their ancestry to a particular geographic area. People in an ethnic group often share certain versions of their genes, which have been passed down from common ancestors. If one of these shared genes contains a disease-causing mutation, a particular genetic disorder may be more frequently seen in the group. Examples of genetic conditions that are more common in particular ethnic groups are sickle cell anemia, which is more common in people of African, African-American, or Mediterranean heritage; and Tay-Sachs disease, which is more likely to occur among people of Ashkenazi (eastern and central European) Jewish or French Canadian ancestry. It is important to note, however, that these disorders can occur in any ethnic group.
Genetic Consultation This section presents information on finding and visiting a genetic counselor or other genetics professional. What Is a Genetic Consultation? A genetic consultation is a health service that provides information and support to people who have, or may be at risk for, genetic disorders. During a consultation, a genetics professional meets with an individual or family to discuss genetic risks or to diagnose, confirm, or rule out a genetic condition. Genetics professionals include medical geneticists (doctors who specialize in genetics) and genetic counselors (certified healthcare workers with experience in medical genetics and counseling). Other healthcare professionals such as nurses, psychologists, and social workers trained in genetics can also provide genetic consultations. Consultations usually take place in a doctor’s office, hospital, genetics center, or other type of medical center. These meetings are most often in-person visits with individuals or families, but they are occasionally conducted in a group or over the telephone.
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Why Might Someone Have a Genetic Consultation? Individuals or families who are concerned about an inherited condition may benefit from a genetic consultation. The reasons that a person might be referred to a genetic counselor, medical geneticist, or other genetics professional include: •
A personal or family history of a genetic condition, birth defect, chromosomal disorder, or hereditary cancer.
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Two or more pregnancy losses (miscarriages), a stillbirth, or a baby who died.
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A child with a known inherited disorder, a birth defect, mental retardation, or developmental delay.
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A woman who is pregnant or plans to become pregnant at or after age 35. (Some chromosomal disorders occur more frequently in children born to older women.)
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Abnormal test results that suggest a genetic or chromosomal condition.
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An increased risk of developing or passing on a particular genetic disorder on the basis of a person’s ethnic background.
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People related by blood (for example, cousins) who plan to have children together. (A child whose parents are related may be at an increased risk of inheriting certain genetic disorders.)
A genetic consultation is also an important part of the decision-making process for genetic testing. A visit with a genetics professional may be helpful even if testing is not available for a specific condition, however. What Happens during a Genetic Consultation? A genetic consultation provides information, offers support, and addresses a patient’s specific questions and concerns. To help determine whether a condition has a genetic component, a genetics professional asks about a person’s medical history and takes a detailed family history (a record of health information about a person’s immediate and extended family). The genetics professional may also perform a physical examination and recommend appropriate tests. If a person is diagnosed with a genetic condition, the genetics professional provides information about the diagnosis, how the condition is inherited, the chance of passing the condition to future generations, and the options for testing and treatment. During a consultation, a genetics professional will: •
Interpret and communicate complex medical information.
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Help each person make informed, independent decisions about their health care and reproductive options.
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Respect each person’s individual beliefs, traditions, and feelings.
A genetics professional will NOT: •
Tell a person which decision to make.
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Advise a couple not to have children.
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Recommend that a woman continue or end a pregnancy.
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Tell someone whether to undergo testing for a genetic disorder. How Can I Find a Genetics Professional in My Area?
To find a genetics professional in your community, you may wish to ask your doctor for a referral. If you have health insurance, you can also contact your insurance company to find a medical geneticist or genetic counselor in your area who participates in your plan. Several resources for locating a genetics professional in your community are available online: •
GeneTests from the University of Washington provides a list of genetics clinics around the United States and international genetics clinics. You can also access the list by clicking on “Clinic Directory” at the top of the GeneTests home page. Clinics can be chosen by state or country, by service, and/or by specialty. State maps can help you locate a clinic in your area. See http://www.genetests.org/.
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The National Society of Genetic Counselors offers a searchable directory of genetic counselors in the United States. You can search by location, name, area of practice/specialization, and/or ZIP Code. See http://www.nsgc.org/resourcelink.cfm.
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The National Cancer Institute provides a Cancer Genetics Services Directory, which lists professionals who provide services related to cancer genetics. You can search by type of cancer or syndrome, location, and/or provider name at the following Web site: http://cancer.gov/search/genetics_services/.
Genetic Testing This section presents information on the benefits, costs, risks, and limitations of genetic testing. What Is Genetic Testing? Genetic testing is a type of medical test that identifies changes in chromosomes, genes, or proteins. Most of the time, testing is used to find changes that are associated with inherited disorders. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder. Several hundred genetic tests are currently in use, and more are being developed. Genetic testing is voluntary. Because testing has both benefits and limitations, the decision about whether to be tested is a personal and complex one. A genetic counselor can help by providing information about the pros and cons of the test and discussing the social and emotional aspects of testing. What Are the Types of Genetic Tests? Genetic testing can provide information about a person’s genes and chromosomes. Available types of testing include:
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•
Newborn screening is used just after birth to identify genetic disorders that can be treated early in life. Millions of babies are tested each year in the United States. All states currently test infants for phenylketonuria (a genetic disorder that causes mental retardation if left untreated) and congenital hypothyroidism (a disorder of the thyroid gland). Most states also test for other genetic disorders.
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Diagnostic testing is used to identify or rule out a specific genetic or chromosomal condition. In many cases, genetic testing is used to confirm a diagnosis when a particular condition is suspected based on physical signs and symptoms. Diagnostic testing can be performed before birth or at any time during a person’s life, but is not available for all genes or all genetic conditions. The results of a diagnostic test can influence a person’s choices about health care and the management of the disorder.
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Carrier testing is used to identify people who carry one copy of a gene mutation that, when present in two copies, causes a genetic disorder. This type of testing is offered to individuals who have a family history of a genetic disorder and to people in certain ethnic groups with an increased risk of specific genetic conditions. If both parents are tested, the test can provide information about a couple’s risk of having a child with a genetic condition.
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Prenatal testing is used to detect changes in a fetus’s genes or chromosomes before birth. This type of testing is offered during pregnancy if there is an increased risk that the baby will have a genetic or chromosomal disorder. In some cases, prenatal testing can lessen a couple’s uncertainty or help them make decisions about a pregnancy. It cannot identify all possible inherited disorders and birth defects, however.
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Preimplantation testing, also called preimplantation genetic diagnosis (PGD), is a specialized technique that can reduce the risk of having a child with a particular genetic or chromosomal disorder. It is used to detect genetic changes in embryos that were created using assisted reproductive techniques such as in-vitro fertilization. In-vitro fertilization involves removing egg cells from a woman’s ovaries and fertilizing them with sperm cells outside the body. To perform preimplantation testing, a small number of cells are taken from these embryos and tested for certain genetic changes. Only embryos without these changes are implanted in the uterus to initiate a pregnancy.
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Predictive and presymptomatic types of testing are used to detect gene mutations associated with disorders that appear after birth, often later in life. These tests can be helpful to people who have a family member with a genetic disorder, but who have no features of the disorder themselves at the time of testing. Predictive testing can identify mutations that increase a person’s risk of developing disorders with a genetic basis, such as certain types of cancer. Presymptomatic testing can determine whether a person will develop a genetic disorder, such as hemochromatosis (an iron overload disorder), before any signs or symptoms appear. The results of predictive and presymptomatic testing can provide information about a person’s risk of developing a specific disorder and help with making decisions about medical care.
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Forensic testing uses DNA sequences to identify an individual for legal purposes. Unlike the tests described above, forensic testing is not used to detect gene mutations associated with disease. This type of testing can identify crime or catastrophe victims, rule out or implicate a crime suspect, or establish biological relationships between people (for example, paternity).
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How Is Genetic Testing Done? Once a person decides to proceed with genetic testing, a medical geneticist, primary care doctor, specialist, or nurse practitioner can order the test. Genetic testing is often done as part of a genetic consultation. Genetic tests are performed on a sample of blood, hair, skin, amniotic fluid (the fluid that surrounds a fetus during pregnancy), or other tissue. For example, a procedure called a buccal smear uses a small brush or cotton swab to collect a sample of cells from the inside surface of the cheek. The sample is sent to a laboratory where technicians look for specific changes in chromosomes, DNA, or proteins, depending on the suspected disorder. The laboratory reports the test results in writing to a person’s doctor or genetic counselor. Newborn screening tests are done on a small blood sample, which is taken by pricking the baby’s heel. Unlike other types of genetic testing, a parent will usually only receive the result if it is positive. If the test result is positive, additional testing is needed to determine whether the baby has a genetic disorder. Before a person has a genetic test, it is important that he or she understands the testing procedure, the benefits and limitations of the test, and the possible consequences of the test results. The process of educating a person about the test and obtaining permission is called informed consent. What Is Direct-to-Consumer Genetic Testing? Traditionally, genetic tests have been available only through healthcare providers such as physicians, nurse practitioners, and genetic counselors. Healthcare providers order the appropriate test from a laboratory, collect and send the samples, and interpret the test results. Direct-to-consumer genetic testing refers to genetic tests that are marketed directly to consumers via television, print advertisements, or the Internet. This form of testing, which is also known as at-home genetic testing, provides access to a person’s genetic information without necessarily involving a doctor or insurance company in the process. If a consumer chooses to purchase a genetic test directly, the test kit is mailed to the consumer instead of being ordered through a doctor’s office. The test typically involves collecting a DNA sample at home, often by swabbing the inside of the cheek, and mailing the sample back to the laboratory. In some cases, the person must visit a health clinic to have blood drawn. Consumers are notified of their results by mail or over the telephone, or the results are posted online. In some cases, a genetic counselor or other healthcare provider is available to explain the results and answer questions. The price for this type of at-home genetic testing ranges from several hundred dollars to more than a thousand dollars. The growing market for direct-to-consumer genetic testing may promote awareness of genetic diseases, allow consumers to take a more proactive role in their health care, and offer a means for people to learn about their ancestral origins. At-home genetic tests, however, have significant risks and limitations. Consumers are vulnerable to being misled by the results of unproven or invalid tests. Without guidance from a healthcare provider, they may make important decisions about treatment or prevention based on inaccurate, incomplete, or misunderstood information about their health. Consumers may also experience an invasion of genetic privacy if testing companies use their genetic information in an unauthorized way.
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Genetic testing provides only one piece of information about a person’s health—other genetic and environmental factors, lifestyle choices, and family medical history also affect a person’s risk of developing many disorders. These factors are discussed during a consultation with a doctor or genetic counselor, but in many cases are not addressed by athome genetic tests. More research is needed to fully understand the benefits and limitations of direct-to-consumer genetic testing. What Do the Results of Genetic Tests Mean? The results of genetic tests are not always straightforward, which often makes them challenging to interpret and explain. Therefore, it is important for patients and their families to ask questions about the potential meaning of genetic test results both before and after the test is performed. When interpreting test results, healthcare professionals consider a person’s medical history, family history, and the type of genetic test that was done. A positive test result means that the laboratory found a change in a particular gene, chromosome, or protein of interest. Depending on the purpose of the test, this result may confirm a diagnosis, indicate that a person is a carrier of a particular genetic mutation, identify an increased risk of developing a disease (such as cancer) in the future, or suggest a need for further testing. Because family members have some genetic material in common, a positive test result may also have implications for certain blood relatives of the person undergoing testing. It is important to note that a positive result of a predictive or presymptomatic genetic test usually cannot establish the exact risk of developing a disorder. Also, health professionals typically cannot use a positive test result to predict the course or severity of a condition. A negative test result means that the laboratory did not find a change in the gene, chromosome, or protein under consideration. This result can indicate that a person is not affected by a particular disorder, is not a carrier of a specific genetic mutation, or does not have an increased risk of developing a certain disease. It is possible, however, that the test missed a disease-causing genetic alteration because many tests cannot detect all genetic changes that can cause a particular disorder. Further testing may be required to confirm a negative result. In some cases, a negative result might not give any useful information. This type of result is called uninformative, indeterminate, inconclusive, or ambiguous. Uninformative test results sometimes occur because everyone has common, natural variations in their DNA, called polymorphisms, that do not affect health. If a genetic test finds a change in DNA that has not been associated with a disorder in other people, it can be difficult to tell whether it is a natural polymorphism or a disease-causing mutation. An uninformative result cannot confirm or rule out a specific diagnosis, and it cannot indicate whether a person has an increased risk of developing a disorder. In some cases, testing other affected and unaffected family members can help clarify this type of result. What Is the Cost of Genetic Testing, and How Long Does It Take to Get the Results? The cost of genetic testing can range from under $100 to more than $2,000, depending on the nature and complexity of the test. The cost increases if more than one test is necessary or if multiple family members must be tested to obtain a meaningful result. For newborn
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screening, costs vary by state. Some states cover part of the total cost, but most charge a fee of $15 to $60 per infant. From the date that a sample is taken, it may take a few weeks to several months to receive the test results. Results for prenatal testing are usually available more quickly because time is an important consideration in making decisions about a pregnancy. The doctor or genetic counselor who orders a particular test can provide specific information about the cost and time frame associated with that test. Will Health Insurance Cover the Costs of Genetic Testing? In many cases, health insurance plans will cover the costs of genetic testing when it is recommended by a person’s doctor. Health insurance providers have different policies about which tests are covered, however. A person interested in submitting the costs of testing may wish to contact his or her insurance company beforehand to ask about coverage. Some people may choose not to use their insurance to pay for testing because the results of a genetic test can affect a person’s health insurance coverage. Instead, they may opt to pay out-of-pocket for the test. People considering genetic testing may want to find out more about their state’s privacy protection laws before they ask their insurance company to cover the costs. What Are the Benefits of Genetic Testing? Genetic testing has potential benefits whether the results are positive or negative for a gene mutation. Test results can provide a sense of relief from uncertainty and help people make informed decisions about managing their health care. For example, a negative result can eliminate the need for unnecessary checkups and screening tests in some cases. A positive result can direct a person toward available prevention, monitoring, and treatment options. Some test results can also help people make decisions about having children. Newborn screening can identify genetic disorders early in life so treatment can be started as early as possible. What Are the Risks and Limitations of Genetic Testing? The physical risks associated with most genetic tests are very small, particularly for those tests that require only a blood sample or buccal smear (a procedure that samples cells from the inside surface of the cheek). The procedures used for prenatal testing carry a small but real risk of losing the pregnancy (miscarriage) because they require a sample of amniotic fluid or tissue from around the fetus. Many of the risks associated with genetic testing involve the emotional, social, or financial consequences of the test results. People may feel angry, depressed, anxious, or guilty about their results. In some cases, genetic testing creates tension within a family because the results can reveal information about other family members in addition to the person who is tested. The possibility of genetic discrimination in employment or insurance is also a concern.
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Genetic testing can provide only limited information about an inherited condition. The test often can’t determine if a person will show symptoms of a disorder, how severe the symptoms will be, or whether the disorder will progress over time. Another major limitation is the lack of treatment strategies for many genetic disorders once they are diagnosed. A genetics professional can explain in detail the benefits, risks, and limitations of a particular test. It is important that any person who is considering genetic testing understand and weigh these factors before making a decision. What Is Genetic Discrimination? Genetic discrimination occurs when people are treated differently by their employer or insurance company because they have a gene mutation that causes or increases the risk of an inherited disorder. People who undergo genetic testing may be at risk for genetic discrimination. The results of a genetic test are normally included in a person’s medical records. When a person applies for life, disability, or health insurance, the insurance company may ask to look at these records before making a decision about coverage. An employer may also have the right to look at an employee’s medical records. As a result, genetic test results could affect a person’s insurance coverage or employment. People making decisions about genetic testing should be aware that when test results are placed in their medical records, the results might not be kept private. Fear of discrimination is a common concern among people considering genetic testing. Several laws at the federal and state levels help protect people against genetic discrimination; however, genetic testing is a fast-growing field and these laws don’t cover every situation. How Does Genetic Testing in a Research Setting Differ from Clinical Genetic Testing? The main differences between clinical genetic testing and research testing are the purpose of the test and who receives the results. The goals of research testing include finding unknown genes, learning how genes work, and advancing our understanding of genetic conditions. The results of testing done as part of a research study are usually not available to patients or their healthcare providers. Clinical testing, on the other hand, is done to find out about an inherited disorder in an individual patient or family. People receive the results of a clinical test and can use them to help them make decisions about medical care or reproductive issues. It is important for people considering genetic testing to know whether the test is available on a clinical or research basis. Clinical and research testing both involve a process of informed consent in which patients learn about the testing procedure, the risks and benefits of the test, and the potential consequences of testing.
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Gene Therapy This section presents information on experimental techniques, safety, ethics, and availability of gene therapy. What Is Gene Therapy? Gene therapy is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs or surgery. Researchers are testing several approaches to gene therapy, including: •
Replacing a mutated gene that causes disease with a healthy copy of the gene.
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Inactivating, or “knocking out,” a mutated gene that is functioning improperly.
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Introducing a new gene into the body to help fight a disease.
Although gene therapy is a promising treatment option for a number of diseases (including inherited disorders, some types of cancer, and certain viral infections), the technique remains risky and is still under study to make sure that it will be safe and effective. Gene therapy is currently only being tested for the treatment of diseases that have no other cures. How Does Gene Therapy Work? Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. If a mutated gene causes a necessary protein to be faulty or missing, gene therapy may be able to introduce a normal copy of the gene to restore the function of the protein. A gene that is inserted directly into a cell usually does not function. Instead, a carrier called a vector is genetically engineered to deliver the gene. Certain viruses are often used as vectors because they can deliver the new gene by infecting the cell. The viruses are modified so they can’t cause disease when used in people. Some types of virus, such as retroviruses, integrate their genetic material (including the new gene) into a chromosome in the human cell. Other viruses, such as adenoviruses, introduce their DNA into the nucleus of the cell, but the DNA is not integrated into a chromosome. The vector can be injected or given intravenously (by IV) directly into a specific tissue in the body, where it is taken up by individual cells. Alternately, a sample of the patient’s cells can be removed and exposed to the vector in a laboratory setting. The cells containing the vector are then returned to the patient. If the treatment is successful, the new gene delivered by the vector will make a functioning protein. Researchers must overcome many technical challenges before gene therapy will be a practical approach to treating disease. For example, scientists must find better ways to deliver genes and target them to particular cells. They must also ensure that new genes are precisely controlled by the body.
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A new gene is injected into an adenovirus vector, which is used to introduce the modified DNA into a human cell. If the treatment is successful, the new gene will make a functional protein.
Is Gene Therapy Safe? Gene therapy is under study to determine whether it could be used to treat disease. Current research is evaluating the safety of gene therapy; future studies will test whether it is an effective treatment option. Several studies have already shown that this approach can have very serious health risks, such as toxicity, inflammation, and cancer. Because the techniques are relatively new, some of the risks may be unpredictable; however, medical researchers, institutions, and regulatory agencies are working to ensure that gene therapy research is as safe as possible. Comprehensive federal laws, regulations, and guidelines help protect people who participate in research studies (called clinical trials). The U.S. Food and Drug Administration (FDA) regulates all gene therapy products in the United States and oversees research in this area. Researchers who wish to test an approach in a clinical trial must first obtain permission from the FDA. The FDA has the authority to reject or suspend clinical trials that are suspected of being unsafe for participants. The National Institutes of Health (NIH) also plays an important role in ensuring the safety of gene therapy research. NIH provides guidelines for investigators and institutions (such as universities and hospitals) to follow when conducting clinical trials with gene therapy. These guidelines state that clinical trials at institutions receiving NIH funding for this type of research must be registered with the NIH Office of Biotechnology Activities. The protocol, or plan, for each clinical trial is then reviewed by the NIH Recombinant DNA Advisory Committee (RAC) to determine whether it raises medical, ethical, or safety issues that warrant further discussion at one of the RAC’s public meetings.
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An Institutional Review Board (IRB) and an Institutional Biosafety Committee (IBC) must approve each gene therapy clinical trial before it can be carried out. An IRB is a committee of scientific and medical advisors and consumers that reviews all research within an institution. An IBC is a group that reviews and approves an institution’s potentially hazardous research studies. Multiple levels of evaluation and oversight ensure that safety concerns are a top priority in the planning and carrying out of gene therapy research. What Are the Ethical Issues surrounding Gene Therapy? Because gene therapy involves making changes to the body’s set of basic instructions, it raises many unique ethical concerns. The ethical questions surrounding gene therapy include: •
How can “good” and “bad” uses of gene therapy be distinguished?
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Who decides which traits are normal and which constitute a disability or disorder?
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Will the high costs of gene therapy make it available only to the wealthy?
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Could the widespread use of gene therapy make society less accepting of people who are different?
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Should people be allowed to use gene therapy to enhance basic human traits such as height, intelligence, or athletic ability?
Current gene therapy research has focused on treating individuals by targeting the therapy to body cells such as bone marrow or blood cells. This type of gene therapy cannot be passed on to a person’s children. Gene therapy could be targeted to egg and sperm cells (germ cells), however, which would allow the inserted gene to be passed on to future generations. This approach is known as germline gene therapy. The idea of germline gene therapy is controversial. While it could spare future generations in a family from having a particular genetic disorder, it might affect the development of a fetus in unexpected ways or have long-term side effects that are not yet known. Because people who would be affected by germline gene therapy are not yet born, they can’t choose whether to have the treatment. Because of these ethical concerns, the U.S. Government does not allow federal funds to be used for research on germline gene therapy in people. Is Gene Therapy Available to Treat My Disorder? Gene therapy is currently available only in a research setting. The U.S. Food and Drug Administration (FDA) has not yet approved any gene therapy products for sale in the United States. Hundreds of research studies (clinical trials) are under way to test gene therapy as a treatment for genetic conditions, cancer, and HIV/AIDS. If you are interested in participating in a clinical trial, talk with your doctor or a genetics professional about how to participate. You can also search for clinical trials online. ClinicalTrials.gov, a service of the National Institutes of Health, provides easy access to information on clinical trials. You can search for specific trials or browse by condition or trial sponsor. You may wish to refer to a list of gene therapy trials that are accepting (or will accept) patients.
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The Human Genome Project and Genomic Research This section presents information on the goals, accomplishments, and next steps in understanding the human genome. What Is a Genome? A genome is an organism’s complete set of DNA, including all of its genes. Each genome contains all of the information needed to build and maintain that organism. In humans, a copy of the entire genome—more than 3 billion DNA base pairs—is contained in all cells that have a nucleus. What Was the Human Genome Project and Why Has It Been Important? The Human Genome Project was an international research effort to determine the sequence of the human genome and identify the genes that it contains. The Project was coordinated by the National Institutes of Health and the U.S. Department of Energy. Additional contributors included universities across the United States and international partners in the United Kingdom, France, Germany, Japan, and China. The Human Genome Project formally began in 1990 and was completed in 2003, 2 years ahead of its original schedule. The work of the Human Genome Project has allowed researchers to begin to understand the blueprint for building a person. As researchers learn more about the functions of genes and proteins, this knowledge will have a major impact in the fields of medicine, biotechnology, and the life sciences. What Were the Goals of the Human Genome Project? The main goals of the Human Genome Project were to provide a complete and accurate sequence of the 3 billion DNA base pairs that make up the human genome and to find all of the estimated 20,000 to 25,000 human genes. The Project also aimed to sequence the genomes of several other organisms that are important to medical research, such as the mouse and the fruit fly. In addition to sequencing DNA, the Human Genome Project sought to develop new tools to obtain and analyze the data and to make this information widely available. Also, because advances in genetics have consequences for individuals and society, the Human Genome Project committed to exploring the consequences of genomic research through its Ethical, Legal, and Social Implications (ELSI) program. What Did the Human Genome Project Accomplish? In April 2003, researchers announced that the Human Genome Project had completed a high-quality sequence of essentially the entire human genome. This sequence closed the gaps from a working draft of the genome, which was published in 2001. It also identified the locations of many human genes and provided information about their structure and
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organization. The Project made the sequence of the human genome and tools to analyze the data freely available via the Internet. In addition to the human genome, the Human Genome Project sequenced the genomes of several other organisms, including brewers’ yeast, the roundworm, and the fruit fly. In 2002, researchers announced that they had also completed a working draft of the mouse genome. By studying the similarities and differences between human genes and those of other organisms, researchers can discover the functions of particular genes and identify which genes are critical for life. The Project’s Ethical, Legal, and Social Implications (ELSI) program became the world’s largest bioethics program and a model for other ELSI programs worldwide. What Were Some of the Ethical, Legal, and Social Implications Addressed by the Human Genome Project? The Ethical, Legal, and Social Implications (ELSI) program was founded in 1990 as an integral part of the Human Genome Project. The mission of the ELSI program was to identify and address issues raised by genomic research that would affect individuals, families, and society. A percentage of the Human Genome Project budget at the National Institutes of Health and the U.S. Department of Energy was devoted to ELSI research. The ELSI program focused on the possible consequences of genomic research in four main areas: •
Privacy and fairness in the use of genetic information, including the potential for genetic discrimination in employment and insurance.
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The integration of new genetic technologies, such as genetic testing, into the practice of clinical medicine.
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Ethical issues surrounding the design and conduct of genetic research with people, including the process of informed consent.
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The education of healthcare professionals, policy makers, students, and the public about genetics and the complex issues that result from genomic research. What Are the Next Steps in Genomic Research?
Discovering the sequence of the human genome was only the first step in understanding how the instructions coded in DNA lead to a functioning human being. The next stage of genomic research will begin to derive meaningful knowledge from the DNA sequence. Research studies that build on the work of the Human Genome Project are under way worldwide. The objectives of continued genomic research include the following: •
Determine the function of genes and the elements that regulate genes throughout the genome.
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Find variations in the DNA sequence among people and determine their significance. These variations may one day provide information about a person’s disease risk and response to certain medications.
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Discover the 3-dimensional structures of proteins and identify their functions.
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Explore how DNA and proteins interact with one another and with the environment to create complex living systems.
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Develop and apply genome-based strategies for the early detection, diagnosis, and treatment of disease.
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Sequence the genomes of other organisms, such as the rat, cow, and chimpanzee, in order to compare similar genes between species.
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Develop new technologies to study genes and DNA on a large scale and store genomic data efficiently.
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Continue to explore the ethical, legal, and social issues raised by genomic research. What Is Pharmacogenomics?
Pharmacogenomics is the study of how genes affect a person’s response to drugs. This relatively new field combines pharmacology (the science of drugs) and genomics (the study of genes and their functions) to develop effective, safe medications and doses that will be tailored to a person’s genetic makeup. Many drugs that are currently available are “one size fits all,” but they don’t work the same way for everyone. It can be difficult to predict who will benefit from a medication, who will not respond at all, and who will experience negative side effects (called adverse drug reactions). Adverse drug reactions are a significant cause of hospitalizations and deaths in the United States. With the knowledge gained from the Human Genome Project, researchers are learning how inherited differences in genes affect the body’s response to medications. These genetic differences will be used to predict whether a medication will be effective for a particular person and to help prevent adverse drug reactions. The field of pharmacogenomics is still in its infancy. Its use is currently quite limited, but new approaches are under study in clinical trials. In the future, pharmacogenomics will allow the development of tailored drugs to treat a wide range of health problems, including cardiovascular disease, Alzheimer disease, cancer, HIV/AIDS, and asthma.
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APPENDIX B. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute16: •
National Institutes of Health (NIH); guidelines consolidated across agencies available at http://health.nih.gov/
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/Publications/FactSheets.htm
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancertopics/pdq
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/health/
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/HealthInformation/Publications/
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/Publications/
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These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidcr.nih.gov/HealthInformation/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/healthinformation/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Biomedical Imaging and Bioengineering; general information at http://www.nibib.nih.gov/HealthEdu
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.17 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic
17
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html).
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citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine18: •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/index.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
18
See http://www.nlm.nih.gov/databases/index.html.
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The NLM Gateway19 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.20 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type Williams syndrome (or synonyms) into the search box and click Search. The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 896 16 56 0 0 968
HSTAT21 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.22 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.23 Simply search by Williams syndrome (or synonyms) at the following Web site: http://text.nlm.nih.gov. Coffee Break: Tutorials for Biologists24 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. 19
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
20
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 21 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 22 23
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration’s Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force’s Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations. 24 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
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Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.25 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.26 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
MD Consult: Access to electronic clinical resources, see http://www.mdconsult.com/.
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Medical Matrix: Lists over 6000 medical Web sites and links to over 1.5 million documents with clinical content, see http://www.medmatrix.org/.
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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Williams Syndrome In the following section, we will discuss databases and references which relate to the Genome Project and Williams syndrome. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).27 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type Williams syndrome (or synonyms) into the search box, and click Go. If too many results appear, you can narrow the search by adding the word clinical. Each report will have
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The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 26 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 27 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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additional links to related research and databases. The following is an example of the results you can obtain from the OMIM for Williams syndrome: •
WILLIAMS-BEUREN SYNDROME CHROMOSOME REGION 1; WBSCR1 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603431
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WILLIAMS-BEUREN SYNDROME CHROMOSOME REGION 14; WBSCR14 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605678
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WILLIAMS-BEUREN SYNDROME CHROMOSOME REGION 5; WBSCR5 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605719 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
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Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
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Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
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Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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GEO DataSets: Curated gene expression and molecular abundance data sets assembled from the Gene Expression Omnibus (GEO) repository, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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GEO Profiles: Individual gene expression and molecular abundance profiles assembled from the Gene Expression Omnibus (GEO) repository, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
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To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/gquery/gquery.fcgi, and then select the database that you would like to search. Or, to search across databases, you can enter Williams syndrome (or synonyms) into the search box and click Go. Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database28 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database29 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the GDB Human Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search All Biological Data by Name/GDB ID. Type Williams syndrome (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word and or or (using or might be useful when using synonyms).
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Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 29 Adapted from the Genome Database: http://www.gdb.org/gdb/aboutGDB.html#mission.
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APPENDIX C. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called Fact Sheets or Guidelines. They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on Williams syndrome can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased services that post them.
Patient Guideline Sources This section directs you to sources which either publish fact sheets or can help you find additional guidelines on topics related to Williams syndrome. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are health topic pages which list links to available materials relevant to Williams syndrome. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for Williams syndrome:
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Connective Tissue Disorders http://www.nlm.nih.gov/medlineplus/connectivetissuedisorders.html Developmental Disabilities http://www.nlm.nih.gov/medlineplus/developmentaldisabilities.html Down Syndrome http://www.nlm.nih.gov/medlineplus/downsyndrome.html Ehlers-Danlos Syndrome http://www.nlm.nih.gov/medlineplus/ehlersdanlossyndrome.html Endocrine Diseases http://www.nlm.nih.gov/medlineplus/endocrinediseases.html Heart Diseases http://www.nlm.nih.gov/medlineplus/heartdiseases.html Leukodystrophies http://www.nlm.nih.gov/medlineplus/leukodystrophies.html Marfan Syndrome http://www.nlm.nih.gov/medlineplus/marfansyndrome.html Metabolic Disorders http://www.nlm.nih.gov/medlineplus/metabolicdisorders.html Neurologic Diseases http://www.nlm.nih.gov/medlineplus/neurologicdiseases.html Parathyroid Disorders http://www.nlm.nih.gov/medlineplus/parathyroiddisorders.html Prader-Willi Syndrome http://www.nlm.nih.gov/medlineplus/praderwillisyndrome.html Turner's Syndrome http://www.nlm.nih.gov/medlineplus/turnerssyndrome.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click Search. This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •
Frequently Asked Questions Source: www.williams-syndrome.org http://www.williams-syndrome.org/forparents/faq.html
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HONselect - Williams Syndrome Source: www.hon.ch http://www.hon.ch/HONselect/RareDiseases/C10.597.606.643.970.html The NIH Search Utility
The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to Williams syndrome. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://health.nih.gov/index.asp. Under Search Health Topics, type Williams syndrome (or synonyms) into the search box, and click Search. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMD®Health: http://www.webmd.com/diseases_and_conditions/default.htm
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Williams syndrome. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Williams syndrome. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about Williams syndrome. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.
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Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://sis.nlm.nih.gov/dirline.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. Simply type in Williams syndrome (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://healthhotlines.nlm.nih.gov/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type Williams syndrome (or a synonym) into the search box, and click Submit Query.
Resources for Patients and Families The following are organizations that provide support and advocacy for patient with genetic conditions and their families30: •
Genetic Alliance: http://geneticalliance.org
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Genetic and Rare Diseases Information Center: http://rarediseases.info.nih.gov/html/resources/info_cntr.html
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Madisons Foundation: http://www.madisonsfoundation.org/
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March of Dimes: http://www.marchofdimes.com
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National Organization for Rare Disorders (NORD): http://www.rarediseases.org/ For More Information on Genetics
The following publications offer detailed information for patients about the science of genetics: •
30
What Is a Genome?: http://www.ncbi.nlm.nih.gov/About/primer/genetics_genome.html
Adapted from the National Library of Medicine: http://ghr.nlm.nih.gov/ghr/resource/patients.
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•
A Science Called Genetics: http://publications.nigms.nih.gov/genetics/science.html
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Genetic Mapping: http://www.genome.gov/10000715
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/archive//20040831/nichsr/ta101/ta10108.html
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on Williams syndrome: •
Basic Guidelines for Williams Syndrome ADD Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001551.htm Williams syndrome Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001116.htm
•
Signs & Symptoms for Williams Syndrome Anxiety Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Epicanthal folds Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003030.htm
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Flattened nasal bridge Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003056.htm Hypercalcemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000365.htm Microcephaly Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003272.htm Pectus excavatum Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003320.htm Short stature Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003271.htm •
Diagnostics and Tests for Williams Syndrome ALT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003473.htm Blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003398.htm ECG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003868.htm Echocardiography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003869.htm Hypercalcemia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003486.htm Ultrasound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003336.htm
•
Background Topics for Williams Syndrome Cardiovascular Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002310.htm Prenatal diagnosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002053.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
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•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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WILLIAMS SYNDROME DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Abscess: A localized, circumscribed collection of pus. [NIH] ACE: Angiotensin-coverting enzyme. A drug used to decrease pressure inside blood vessels. [NIH]
Actin: Essential component of the cell skeleton. [NIH] Acuity: Clarity or clearness, especially of the vision. [EU] Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with
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similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Alexia: The inability to recognize or comprehend written or printed words. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]
Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve
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function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anti-infective: An agent that so acts. [EU] Anuria: Inability to form or excrete urine. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Coarctation: Narrowing of the lumen of the aorta, caused by deformity of the aortic media. [NIH] Aortic Stenosis, Supravalvular: A narrowing of the aorta in the region above the aortic
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valve. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriosus: Circle composed of anastomosing arteries derived from two long posterior ciliary and seven anterior ciliary arteries, located in the ciliary body about the root of the iris. [NIH]
Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Artificial Organs: Devices intended to replace non-functioning organs. They may be temporary or permanent. Since they are intended always to function as the natural organs they are replacing, they should be differentiated from prostheses and implants and specific types of prostheses which, though also replacements for body parts, are frequently cosmetic (artificial eye) as well as functional (artificial limbs). [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU]
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Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Auditory Cortex: Area of the temporal lobe concerned with hearing. [NIH] Auditory Perception: The process whereby auditory stimuli are selected, organized and interpreted by the organism; includes speech discrimination. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH]
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Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Cardiac: Having to do with the heart. [NIH]
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Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell Movement: The movement of cells from one location to another. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centromere: The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in
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man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chromosome Breakage: A type of chromosomal aberration which may result from spontaneous or induced breakage. Alkylating agents, various types of irradiation, and chemical mutagens have been found to cause induced chromosomal breakage. Breakage can induce base pair translocations, deletions, or chromatid breakage. [NIH] Chromosome Deletion: Actual loss of a portion of the chromosome. [NIH] Chromosome Fragility: Susceptibility of chromosomes to breakage and translocation or other aberrations. Chromosome fragile sites are regions that show up in karyotypes as a gap (uncondensed stretch) on the chromatid arm. They are associated with chromosome break sites and other aberrations. A fragile site on the X chromosome is associated with fragile X syndrome. Fragile sites are designated by the letters "FRA" followed by the designation for the specific chromosome and a letter which refers to the different fragile sites on a chromosome (e.g. FRAXA). [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH]
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Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [NIH] Communication Disorders: Disorders of verbal and nonverbal communication caused by receptive or expressive language disorders, cognitive dysfunction (e.g., mental retardation), psychiatric conditions, and hearing disorders. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements,
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megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Concentric: Having a common center of curvature or symmetry. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]
Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Conus: A large, circular, white patch around the optic disk due to the exposing of the sclera as a result of degenerative change or congenital abnormality in the choroid and retina. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH]
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Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpus: The body of the uterus. [NIH] Corpus Callosum: Broad plate of dense myelinated fibers that reciprocally interconnect regions of the cortex in all lobes with corresponding regions of the opposite hemisphere. The corpus callosum is located deep in the longitudinal fissure. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortices: The outer layer of an organ; used especially of the cerebrum and cerebellum. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with longitudinal studies which are followed over a period of time. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH]
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Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Death Certificates: Official records of individual deaths including the cause of death certified by a physician, and any other required identifying information. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are
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the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diverticula: Plural form of diverticulum. [NIH] Diverticulitis: Inflammation of a diverticulum or diverticula. [NIH] Diverticulum: A pathological condition manifested as a pouch or sac opening from a tubular or sacular organ. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dreams: A series of thoughts, images, or emotions occurring during sleep which are dissociated from the usual stream of consciousness of the waking state. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH]
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Duct: A tube through which body fluids pass. [NIH] Dysgenesis: Defective development. [EU] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may be read but not understood. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elastin: The protein that gives flexibility to tissues. [NIH] Electroencephalography: Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. [NIH] Electrolytes: Substances that break up into ions (electrically charged particles) when they are dissolved in body fluids or water. Some examples are sodium, potassium, chloride, and calcium. Electrolytes are primarily responsible for the movement of nutrients into cells, and the movement of wastes out of cells. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energy Intake: Total number of calories taken in daily whether ingested or by parenteral routes. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory
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systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithalamus: The dorsal posterior subdivision of the diencephalon. The epithalamus is generally considered to include the habenular nuclei (habenula) and associated fiber bundles, the pineal body, and the epithelial roof of the third ventricle. The anterior and posterior paraventricular nuclei of the thalamus are included with the thalamic nuclei although they develop from the same pronuclear mass as the epithalamic nuclei and are sometimes considered part of the epithalamus. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excrete: To get rid of waste from the body. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Eye Color: Color of the iris. [NIH] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which
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occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Eye Movements: Voluntary or reflex-controlled movements of the eye. [NIH] Facial: Of or pertaining to the face. [EU] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [NIH] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Facial Nerve Diseases: Diseases of the facial nerve or nuclei. Pontine disorders may affect the facial nuclei or nerve fascicle. The nerve may be involved intracranially, along its course through the petrous portion of the temporal bone, or along its extracranial course. Clinical manifestations include facial muscle weakness, loss of taste from the anterior tongue, hyperacusis, and decreased lacrimation. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fathers: Male parents, human or animal. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flexion: In gynaecology, a displacement of the uterus in which the organ is bent so far forward or backward that an acute angle forms between the fundus and the cervix. [EU]
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Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]
Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Duplication: It encodes the major envelope protein and includes all the specifications for HBsAg. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Products, rev: Trans-acting nuclear proteins whose functional expression are required
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for HIV viral replication. Specifically, the rev gene products are required for processing and translation of the HIV gag and env mRNAs, and thus rev regulates the expression of the viral structural proteins. rev can also regulate viral regulatory proteins. A cis-acting antirepression sequence (CAR) in env, also known as the rev-responsive element (RRE), is responsive to the rev gene product. rev is short for regulator of virion. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genes, env: DNA sequences that form the coding region for the viral envelope (env) proteins in retroviruses. The env genes contain a cis-acting RNA target sequence for the rev protein (= gene products, rev), termed the rev-responsive element (RRE). [NIH] Genetic Screening: Searching a population or individuals for persons possessing certain genotypes or karyotypes that: (1) are already associated with disease or predispose to disease; (2) may lead to disease in their descendants; or (3) produce other variations not known to be associated with disease. Genetic screening may be directed toward identifying phenotypic expression of genetic traits. It includes prenatal genetic screening. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germline mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; germline mutations are passed on from parents to offspring. Also called hereditary mutation. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Guanine: One of the four DNA bases. [NIH]
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Gyrus Cinguli: One of the convolutions on the medial surface of the cerebral hemisphere. It surrounds the rostral part of the brain and interhemispheric commissure and forms part of the limbic system. [NIH] Hair Color: Color of hair or fur. [NIH] Happiness: Highly pleasant emotion characterized by outward manifestations of gratification; joy. [NIH] Hearing Disorders: Conditions that impair the transmission or perception of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Helix-loop-helix: Regulatory protein of cell cycle. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Hereditary mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; hereditary mutations are passed on from parents to offspring. Also called germline mutation. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Hippocampus: A curved elevation of gray matter extending the entire length of the floor of
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the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hyperacusis: An abnormally disproportionate increase in the sensation of loudness in response to auditory stimuli of normal volume. Cochlear diseases; vestibulocochlear nerve diseases; facial nerve diseases; stapes surgery; and other disorders may be associated with this condition. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypochlorous Acid: HClO. An oxyacid of chlorine containing monovalent chlorine that acts as an oxidizing or reducing agent. [NIH] Hypophysis: A remnant of the entodermal pouch of Rathke beneath the mucous membrane of the pharynx, which shows pituitary tissue. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Immune response: The activity of the immune system against foreign substances (antigens).
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[NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunoglobulins: Glycoproteins present in the blood (antibodies) and in other tissue. They are classified by structure and activity into five classes (IgA, IgD, IgE, IgG, IgM). [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infantile: Pertaining to an infant or to infancy. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH]
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Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Internal Capsule: White matter pathway, flanked by nuclear masses, consisting of both afferent and efferent fibers projecting between the cerebral cortex and the brainstem. It consists of three distinct parts: an anterior limb, posterior limb, and genu. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intracellular: Inside a cell. [NIH] Intravascular: Within a vessel or vessels. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Karyotype: The characteristic chromosome complement of an individual, race, or species as
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defined by their number, size, shape, etc. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Lactation: The period of the secretion of milk. [EU] Language Development: The gradual expansion in complexity and meaning of symbols and sounds as perceived and interpreted by the individual through a maturational and learning process. Stages in development include babbling, cooing, word imitation with cognition, and use of short sentences. [NIH] Language Disorders: Conditions characterized by deficiencies of comprehension or expression of written and spoken forms of language. These include acquired and developmental disorders. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukemia: Cancer of blood-forming tissue. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU]
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Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linkages: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy
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based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malformation: A morphologic developmental process. [EU]
defect
resulting
from
an
intrinsically
abnormal
Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammography: Radiographic examination of the breast. [NIH] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megakaryocytes: Very large bone marrow cells which release mature blood platelets. [NIH] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH]
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Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Miscarriage: Spontaneous expulsion of the products of pregnancy before the middle of the second trimester. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Mosaicism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single zygote, as opposed to chimerism in which the different cell populations are derived from more than one zygote. [NIH] Motility: The ability to move spontaneously. [EU] Motion Perception: The real or apparent movement of objects through the visual field. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular
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sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Nephropathy: Disease of the kidneys. [EU] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Pathways: Neural tracts connecting one part of the nervous system with another. [NIH]
Neurologic: Having to do with nerves or the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel
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across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrophil: A type of white blood cell. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Envelope: The membrane system of the cell nucleus that surrounds the nucleoplasm. It consists of two concentric membranes separated by the perinuclear space. The structures of the envelope where it opens to the cytoplasm are called the nuclear pores (nuclear pore). [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleosomes: The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Occipital Lobe: Posterior part of the cerebral hemisphere. [NIH] Octamer: Eight molecules of histone. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or
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allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Oxidative Phosphorylation: Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pamidronate: A drug that belongs to the family of drugs called bisphosphonates. Pamidronate is used as treatment for abnormally high levels of calcium in the blood. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Paradoxical: Occurring at variance with the normal rule. [EU] Paralysis: Loss of ability to move all or part of the body. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH]
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Paternity: Establishing the father relationship of a man and a child. [NIH] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] PDQ: Physician Data Query. PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information is available on the CancerNet Web site, and more specific information about PDQ can be found at http://cancernet.nci.nih.gov/pdq.html. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perirhinal: Transitional region between the older and newer cortex. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phobias: An exaggerated and invariably pathological dread of some specific type of stimulus or situation. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase
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"physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis,
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therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presumptive: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the
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nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pseudogenes: Genes bearing close resemblance to known genes at different loci, but rendered non-functional by additions or deletions in structure that prevent normal transcription or translation. When lacking introns and containing a poly-A segment near the downstream end (as a result of reverse copying from processed nuclear RNA into doublestranded DNA), they are called processed genes. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Psychophysics: The science dealing with the correlation of the physical characteristics of a stimulus, e.g., frequency or intensity, with the response to the stimulus, in order to assess the psychologic factors involved in the relationship. [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation
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therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reentry: Reexcitation caused by continuous propagation of the same impulse for one or more cycles. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH] Research Support: Financial support of research activities. [NIH] Restless legs: Legs characterized by or showing inability to remain at rest. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoblastoma Protein: Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein. [NIH]
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Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhabdoid tumor: A malignant tumor of either the central nervous system (CNS) or the kidney. Malignant rhabdoid tumors of the CNS often have an abnormality of chromosome 22. These tumors usually occur in children younger than 2 years. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Robotics: The application of electronic, computerized control systems to mechanical devices designed to perform human functions. Formerly restricted to industry, but nowadays applied to artificial organs controlled by bionic (bioelectronic) devices, like automated insulin pumps and other prostheses. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Sella Turcica: A bony prominence situated on the upper surface of the body of the sphenoid bone. It houses the pituitary gland. [NIH] Semantics: The relationships between symbols and their meanings. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septal Nuclei: Neural nuclei situated in the septal region. They have afferent and cholinergic efferent connections with a variety of forebrain and brainstem areas including
Dictionary 189
the hippocampus, the lateral hypothalamus, the tegmentum, and the amygdala. Included are the dorsal, lateral, medial, and triangular septal nuclei, septofimbrial nucleus, nucleus of diagonal band, nucleus of anterior commissure, and the nucleus of stria terminalis. [NIH] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Sociability: The tendency of organisms to grow together with others of the same kind. [NIH] Social Behavior: Any behavior caused by or affecting another individual, usually of the
190
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same species. [NIH] Social Perception: The perceiving of attributes, characteristics, and behaviors of one's associates or social groups. [NIH] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somatic mutations: Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphenoid: An unpaired cranial bone with a body containing the sphenoid sinus and forming the posterior part of the medial walls of the orbits. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stenosis: Narrowing or stricture of a duct or canal. [EU] Stent: A device placed in a body structure (such as a blood vessel or the gastrointestinal tract) to provide support and keep the structure open. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Stillbirth: The birth of a dead fetus or baby. [NIH]
Dictionary 191
Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Striate: Recurrent branch of the anterior cerebral artery which supplies the anterior limb of the internal capsule. [NIH] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Stromal Cells: Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH]
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Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synchrony: The normal physiologic sequencing of atrial and ventricular activation and contraction. [NIH] Synostosis: The joining of contiguous and separate bones by osseous tissue. [NIH] Syrinx: A fistula. [NIH] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [NIH] Temperament: Predisposition to react to one's environment in a certain way; usually refers to mood changes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]
Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH]
Dictionary 193
Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH]
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Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Trinucleotide Repeat Expansion: DNA region comprised of a variable number of repetitive, contiguous trinucleotide sequences. The presence of these regions is associated with diseases such as Fragile X Syndrome and myotonic dystrophy. Many chromosome fragile sites (chromosome fragility) contain expanded trinucleotide repeats. [NIH] Trinucleotide Repeats: Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]
Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tubulin: A microtubule subunit protein found in large quantities in mammalian brain. It has also been isolated from sperm flagella, cilia, and other sources. Structurally, the protein is a dimer with a molecular weight of approximately 120,000 and a sedimentation coefficient of 5.8S. It binds to colchicine, vincristine, and vinblastine. [NIH] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ultraviolet radiation: Invisible rays that are part of the energy that comes from the sun. UV radiation can damage the skin and cause melanoma and other types of skin cancer. UV radiation that reaches the earth's surface is made up of two types of rays, called UVA and UVB rays. UVB rays are more likely than UVA rays to cause sunburn, but UVA rays pass deeper into the skin. Scientists have long thought that UVB radiation can cause melanoma and other types of skin cancer. They now think that UVA radiation also may add to skin damage that can lead to skin cancer and cause premature aging. For this reason, skin specialists recommend that people use sunscreens that reflect, absorb, or scatter both kinds of UV radiation. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH]
Dictionary 195
Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venter: Belly. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visual Cortex: Area of the occipital lobe concerned with vision. [NIH]
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Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Vocal cord: The vocal folds of the larynx. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
197
INDEX 3 3-dimensional, 45, 106, 137, 154 A Abdomen, 154, 177, 182, 183, 191, 195 Aberrant, 32, 154 Abscess, 154, 188 ACE, 61, 154 Actin, 19, 20, 107, 154 Acuity, 45, 154 Acute lymphoblastic leukemia, 84, 154 Acute lymphocytic leukemia, 154 Adaptability, 154, 160 Adaptation, 154, 184 Adenine, 100, 154, 186 Adenosine, 101, 154, 183 Adenosine Triphosphate, 101, 154, 183 Adenovirus, 133, 154, 187 Adolescence, 40, 154 Adrenergic, 154, 166, 168, 191 Adverse Effect, 155, 189 Aerobic, 155, 179 Agonist, 155, 166 Alexia, 155, 167 Algorithms, 25, 155, 158 Alkaline, 155, 159 Alleles, 102, 119, 155 Alpha-1, 115, 119, 155 Alternative medicine, 155 Amino Acid Sequence, 155, 156 Amino Acids, 102, 106, 112, 155, 162, 183, 184, 185, 188, 194 Amnion, 155 Amniotic Fluid, 128, 130, 155 Amygdala, 26, 32, 46, 155, 158, 177, 189, 192 Anaesthesia, 49, 72, 78, 155, 174 Anal, 50, 155, 169, 177 Anatomical, 26, 29, 155, 157, 161, 174, 188 Anemia, 114, 115, 118, 119, 124, 144, 155 Anesthesia, 52, 55, 155, 167 Aneuploidy, 112, 113, 156 Aneurysm, 58, 156 Angiography, 49, 156 Angioplasty, 50, 61, 156 Anomalies, 24, 38, 55, 86, 92, 156 Anterior Cerebral Artery, 156, 191 Antibacterial, 156, 190 Antibiotic, 156, 190 Antibodies, 15, 107, 156, 174, 184
Antibody, 107, 156, 162, 173, 174, 175, 187 Anticoagulant, 156, 185 Antigen, 156, 162, 173, 174, 187 Anti-infective, 156, 173 Anuria, 156, 176 Anus, 155, 156, 162, 175 Anxiety, 4, 93, 151, 156 Aorta, 4, 54, 64, 156, 195 Aortic Coarctation, 82, 156 Aortic Stenosis, Supravalvular, 156 Apoptosis, 101, 110, 157 Aqueous, 157, 158, 164, 167, 173 Arginine, 157, 173 Arterial, 56, 59, 157, 173, 185, 192 Arteries, 87, 156, 157, 159, 164, 180 Arterioles, 157, 159 Arteriosus, 157, 186 Artery, 36, 55, 58, 72, 80, 84, 156, 157, 164, 167 Articular, 157 Artificial Organs, 157, 188 Astrocytes, 157 Astrocytoma, 77, 157 Ataxia, 143, 144, 157, 192 Atrial, 36, 157, 192 Atrioventricular, 54, 157 Atrium, 157, 195 Atrophy, 143, 158 Atypical, 34, 38, 42, 56, 70, 87, 123, 158 Auditory, 24, 27, 37, 75, 82, 158, 172, 173 Auditory Cortex, 82, 158 Auditory Perception, 75, 158 B Bacteria, 21, 99, 107, 111, 156, 158, 168, 179, 187, 190, 193, 194 Basal Ganglia, 157, 158, 177 Basal Ganglia Diseases, 157, 158 Base Sequence, 111, 158, 170 Basement Membrane, 158, 168 Bewilderment, 158, 163 Bilateral, 27, 51, 77, 93, 158 Bile, 158, 177 Biochemical, 23, 37, 115, 155, 158, 176 Biological Transport, 158, 165 Biotechnology, 5, 47, 96, 106, 133, 135, 140, 142, 143, 144, 145, 158 Bipolar Disorder, 34, 158 Bladder, 159, 170, 185, 194 Blastocyst, 159, 163
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Williams Syndrome
Blood Coagulation, 159, 193 Blood Glucose, 159, 172 Blood pressure, 4, 22, 59, 60, 118, 152, 159, 160, 173, 179 Body Fluids, 159, 167 Bone Marrow, 8, 84, 134, 154, 159, 171, 177, 178, 191 Bone Marrow Cells, 84, 159, 178 Brain Stem, 159, 160 Buccal, 128, 130, 159 Bypass, 54, 159 C Calcium, 4, 159, 162, 167, 173, 182, 189 Carbohydrate, 159, 189 Carbon Dioxide, 159, 169 Carcinogenic, 159, 174, 175 Carcinogens, 159, 182 Cardiac, 35, 38, 52, 72, 92, 159, 168, 180, 191 Cardiovascular, 3, 4, 52, 54, 55, 56, 58, 63, 77, 85, 87, 92, 137, 152, 160 Cardiovascular disease, 4, 56, 63, 137, 160 Case report, 10, 50, 52, 77, 85, 160 Catecholamine, 160, 166 Catheterization, 156, 160 Caudal, 26, 160, 173, 184 Causal, 36, 37, 160 Cause of Death, 160, 165 Cell Cycle, 44, 109, 110, 160, 172 Cell Death, 110, 157, 160, 180 Cell Differentiation, 160, 189 Cell Division, 11, 19, 102, 109, 110, 122, 123, 143, 158, 160, 164, 175, 178, 179, 184, 185, 188 Cell Movement, 19, 160 Cell proliferation, 15, 160, 187, 189 Cell Respiration, 160, 179 Central Nervous System, 25, 160, 165, 170, 179, 188 Centromere, 102, 105, 160 Cerebellar, 52, 59, 157, 160, 187 Cerebellum, 51, 84, 160, 164, 187 Cerebral, 26, 49, 69, 156, 157, 158, 159, 160, 161, 168, 169, 172, 175, 181, 182, 192 Cerebral Cortex, 26, 157, 160, 168, 169, 175 Cerebrovascular, 158, 160, 161, 192 Cerebrum, 160, 161, 164, 192, 194 Cervix, 161, 169 Chest Pain, 4, 161 Chin, 161, 178 Chlorine, 161, 173 Cholesterol, 101, 158, 161, 164
Chromatin, 31, 35, 44, 48, 86, 157, 161, 177, 181 Chromosome Breakage, 35, 161 Chromosome Deletion, 6, 33, 161 Chromosome Fragility, 161, 194 Chronic, 21, 23, 35, 89, 143, 161, 167, 174, 176, 184, 191 Chronic renal, 161, 184 Cirrhosis, 161, 172 CIS, 161, 171 Clinical Medicine, 136, 162, 185 Clinical trial, 24, 133, 134, 137, 140, 162, 163, 183, 185 Cloning, 158, 162 Codon, 107, 162 Cofactor, 162, 185, 193 Colon, 116, 143, 162, 176 Colonoscopy, 118, 162 Communication Disorders, 43, 70, 79, 84, 139, 162 Complement, 162, 163, 175 Complementary medicine, 91, 163 Computational Biology, 140, 142, 163 Concentric, 163, 181 Conception, 109, 163, 169, 190 Conduction, 24, 163 Confusion, 116, 163, 166, 194 Connective Tissue, 4, 13, 147, 159, 163, 169, 170, 191 Connective Tissue Cells, 163 Consciousness, 163, 165, 166 Constitutional, 10, 163 Constriction, 102, 105, 163, 175 Consultation, 27, 124, 125, 128, 129, 163 Continuum, 33, 163 Contraindications, ii, 163 Contrast medium, 156, 163 Control group, 30, 44, 163 Conus, 163, 186 Coordination, 4, 160, 163 Coronary, 55, 58, 61, 80, 84, 160, 164, 180 Coronary heart disease, 160, 164 Coronary Thrombosis, 164, 180 Corpus, 55, 74, 164, 192 Corpus Callosum, 74, 164, 192 Cortex, 26, 28, 29, 32, 48, 53, 54, 62, 71, 72, 164, 167, 183, 187 Cortical, 32, 38, 46, 48, 85, 87, 164, 188, 192 Cortices, 26, 164, 172 Cranial, 88, 160, 164, 169, 190, 195 Crossing-over, 164, 187 Cross-Sectional Studies, 31, 164
Index 199
Cues, 41, 164 Curative, 164, 192 Cytochrome, 164, 182 Cytogenetics, 24, 34, 57, 65, 76, 164 Cytoplasm, 99, 100, 101, 107, 157, 164, 165, 171, 177, 181, 188 Cytosine, 100, 164, 186 Cytoskeleton, 11, 12, 19, 165, 179 Cytotoxic, 165, 189 D De novo, 11, 55, 110, 165 Death Certificates, 118, 165 Deletion, 4, 8, 9, 12, 13, 15, 17, 18, 22, 25, 26, 31, 33, 36, 37, 38, 47, 56, 65, 68, 69, 73, 87, 112, 157, 165, 170 Dementia, 113, 165 Dendrites, 165, 180 Dendritic, 12, 165, 178 Dentate Gyrus, 165, 173 Deoxyribonucleic, 100, 165, 188 Deoxyribonucleic acid, 100, 165, 188 Deoxyribonucleotides, 165 Depolarization, 165, 189 Deuterium, 165, 173 Dextroamphetamine, 165, 179 Diabetes Mellitus, 165, 172, 175 Diastolic, 165, 173 Diffusion, 32, 38, 46, 47, 158, 165 Digestion, 158, 165, 177, 191, 195 Digestive tract, 4, 165, 189 Dilation, 50, 166 Diploid, 156, 166, 179, 184, 194 Direct, iii, 26, 32, 128, 129, 130, 162, 166, 187, 191 Discrimination, 29, 130, 131, 136, 158, 166 Disinfectant, 21, 166 Disorientation, 163, 166 Dissection, 15, 166 Dissociation, 39, 46, 61, 62, 76, 82, 84, 88, 166 Dissociative Disorders, 166 Distal, 33, 166, 186 Diverticula, 166 Diverticulitis, 84, 166 Diverticulum, 166 Dopamine, 40, 165, 166, 181, 183 Dorsal, 26, 37, 39, 42, 57, 61, 62, 75, 166, 168, 184, 189 Dorsum, 166 Dreams, 95, 166 Drive, 35, 166 Duct, 160, 167, 188, 190
Dysgenesis, 76, 167 Dyslexia, 30, 167 Dysplasia, 35, 144, 167 Dystrophy, 24, 143, 167 E Elastic, 13, 14, 58, 84, 167, 190 Elastin, 13, 14, 15, 31, 56, 58, 59, 65, 89, 167 Electroencephalography, 46, 167 Electrolytes, 158, 167, 176 Electrons, 158, 167, 175, 186 Embryo, 109, 110, 111, 119, 155, 159, 160, 167, 174 Empirical, 24, 167 Emulsion, 167, 169 Endarterectomy, 156, 167 Endogenous, 166, 167, 193 End-stage renal, 161, 167, 184 Energy Intake, 51, 167 Enhancer, 18, 37, 167 Entorhinal Cortex, 167, 173 Environmental Exposure, 168, 182 Environmental Health, 25, 139, 140, 168 Enzymatic, 159, 162, 168 Enzyme, 21, 101, 107, 154, 168, 171, 185, 189, 193, 196 Epinephrine, 154, 166, 168, 181, 194 Epithalamus, 168, 177 Epithelial, 20, 158, 168, 182 Epithelial Cells, 20, 168 Erythrocytes, 155, 159, 168 Esophagus, 166, 168, 191 Essential Tremor, 143, 168 Ethnic Groups, 124, 127, 168 Eukaryotic Cells, 168, 174, 182 Evoke, 168, 191 Excrete, 156, 168, 176 Extracellular, 13, 157, 163, 168 Extracellular Matrix, 13, 163, 168 Extracellular Space, 168 Extrapyramidal, 166, 168 Eye Color, 111, 168 Eye Infections, 154, 168 Eye Movements, 29, 169 F Facial, 3, 4, 9, 17, 27, 37, 46, 61, 78, 92, 169, 173 Facial Expression, 37, 46, 169 Facial Nerve, 169, 173 Facial Nerve Diseases, 169, 173 Family Planning, 140, 169 Fat, 159, 164, 169, 190 Fathers, 119, 169
200
Williams Syndrome
Fatigue, 169, 172 Fetus, 127, 128, 130, 134, 169, 185, 190, 194 Fibrosis, 111, 114, 118, 119, 144, 169, 188 Fissure, 49, 164, 165, 169 Fistula, 169, 192 Fixation, 30, 169 Flexion, 39, 169 Fluorescence, 25, 34, 36, 170 Fold, 169, 170 Forearm, 159, 170 Fossa, 160, 170 Fovea, 169, 170 Frameshift, 112, 170 Frameshift Mutation, 112, 170 Free Radicals, 166, 170 Functional magnetic resonance imaging, 27, 38, 39, 43, 46, 170 Fundus, 169, 170 G Ganglia, 158, 170, 180 Gas, 159, 161, 165, 170, 173, 181 Gastrin, 170, 173 Gastrointestinal, 168, 170, 190 Gastrointestinal tract, 170, 190 Gene Deletion, 9, 10, 58, 59, 170 Gene Duplication, 24, 170 Gene Expression, 18, 32, 44, 47, 107, 108, 144, 170, 171 Gene Products, rev, 170, 171 Gene Therapy, 132, 133, 134, 154, 171 Genes, env, 118, 171 Genetic Screening, 24, 171 Genetic testing, 121, 125, 126, 127, 128, 129, 130, 131, 136, 171 Genomics, 7, 14, 18, 21, 31, 60, 64, 66, 79, 89, 137, 171 Genotype, 7, 15, 16, 17, 19, 21, 40, 64, 90, 171, 183 Germ Cells, 110, 134, 171, 178, 182, 190 Germline mutation, 110, 171, 172 Gland, 171, 182, 184, 185, 188, 191, 193 Glucose, 143, 159, 165, 171, 172, 175 Governing Board, 171, 185 Grafting, 171, 174 Granule, 165, 171, 188 Granulocytes, 171, 176, 189, 196 Guanine, 100, 171, 186 Gyrus Cinguli, 156, 172, 177 H Hair Color, 111, 172 Happiness, 89, 172 Hearing Disorders, 162, 172
Heart attack, 160, 172 Heart failure, 4, 172 Heartbeat, 172, 191 Helix-loop-helix, 37, 172 Hemochromatosis, 127, 172 Hemodialysis, 172, 176 Hemoglobin, 101, 155, 168, 172 Hemoglobinopathies, 171, 172 Hemoglobinuria, 143, 172 Hemophilia, 119, 144, 172 Hemorrhage, 172, 191 Hereditary, 24, 99, 100, 110, 119, 125, 171, 172, 187 Hereditary mutation, 110, 171, 172 Heredity, 102, 170, 171, 172 Heterogeneity, 53, 172 Hippocampus, 32, 36, 165, 172, 177, 189, 191 Histones, 102, 161, 173, 181 Homogeneous, 163, 173 Homologous, 23, 155, 164, 171, 173, 188, 191, 192 Hormonal, 158, 173 Hormone, 107, 168, 170, 173, 175, 189, 193 Human Development, 35, 39, 40, 139, 173 Hybrid, 173 Hybridization, 33, 173 Hydrogen, 21, 158, 159, 165, 173, 179, 181, 186 Hydrogen Peroxide, 21, 173 Hyperacusis, 50, 62, 65, 66, 93, 95, 169, 173 Hypercalcemia, 4, 36, 84, 152, 173 Hypertension, 4, 5, 22, 23, 59, 79, 160, 173, 193 Hypochlorous Acid, 21, 173 Hypophysis, 173, 188 Hypoplasia, 51, 173 Hypothalamus, 26, 173, 177, 184, 189, 192 I Immune response, 156, 173, 195 Immune system, 8, 15, 21, 44, 173, 174, 177, 194, 196 Immunodeficiency, 143, 174 Immunoglobulins, 44, 174 Impairment, 27, 60, 79, 86, 96, 157, 158, 169, 174, 178, 179 Implantation, 36, 163, 174 In situ, 34, 36, 73, 174 In Situ Hybridization, 34, 36, 73, 174 In vitro, 45, 171, 174 In vivo, 35, 45, 171, 174 Incision, 174, 175
Index 201
Induction, 25, 27, 30, 174 Infancy, 4, 28, 31, 36, 137, 174 Infantile, 68, 84, 174 Infarction, 174 Infection, 15, 168, 174, 177, 180, 191, 196 Infertility, 33, 174 Inflammation, 133, 166, 169, 174, 182, 184 Informed Consent, 128, 131, 136, 174 Initiation, 174, 193 Initiator, 17, 175 Inotropic, 166, 175 Insight, 45, 46, 175 Insulin, 175, 188 Internal Capsule, 156, 175, 191 Interphase, 24, 175 Interstitial, 33, 68, 69, 168, 175 Intestinal, 175, 178 Intestines, 170, 175, 188 Intracellular, 174, 175, 189 Intravascular, 62, 175 Introns, 175, 186 Invasive, 20, 175, 177 Involuntary, 158, 168, 175, 180, 187, 190 Ions, 158, 166, 167, 173, 175 Iris, 157, 168, 175, 186 Irradiation, 161, 175 Ischemia, 158, 175 K Karyotype, 5, 104, 175 Kb, 66, 176 Kidney Disease, 139, 144, 176 Kidney Failure, 113, 167, 176 Kidney Failure, Acute, 176 Kidney Failure, Chronic, 176 Kinetics, 35, 176 L Lactation, 91, 176 Language Development, 48, 176 Language Disorders, 96, 162, 176 Large Intestine, 166, 175, 176, 187, 189 Larynx, 176, 193, 196 Latency, 37, 176 Lesion, 176, 177 Leucocyte, 155, 176, 177 Leukemia, 8, 35, 45, 143, 171, 176 Ligament, 176, 185 Limbic, 32, 47, 155, 172, 177 Limbic System, 32, 47, 155, 172, 177 Linkages, 32, 172, 173, 177 Liver, 108, 158, 161, 167, 172, 177 Lobe, 29, 156, 177 Localization, 12, 25, 60, 177
Localized, 154, 169, 174, 177, 184 Longitudinal Studies, 164, 177 Longitudinal study, 31, 48, 84, 177 Loop, 177 Lymphatic, 174, 177 Lymphoblastic, 177 Lymphoblasts, 154, 177 Lymphocytes, 156, 176, 177, 196 Lymphoid, 156, 176, 177 Lymphoma, 52, 76, 77, 143, 177 Lysine, 173, 177 M Macrophage, 110, 177 Magnetic Resonance Imaging, 32, 34, 83, 177 Malabsorption, 143, 178 Malformation, 33, 178 Malignancy, 52, 178 Malignant, 10, 35, 143, 178, 188 Malignant tumor, 178, 188 Malnutrition, 158, 178, 180 Mammography, 118, 178 Manic, 158, 178 Manifest, 40, 178 Medial, 29, 72, 172, 178, 182, 189, 190 Mediate, 37, 166, 178 Medical Records, 118, 131, 178 MEDLINE, 140, 142, 144, 178 Megakaryocytes, 159, 178 Meiosis, 109, 178, 191, 192 Melanin, 175, 178, 183, 194 Melanocytes, 178 Melanoma, 19, 20, 143, 178, 194 Membrane, 100, 155, 157, 162, 165, 168, 173, 176, 178, 181, 182, 189 Memory, 24, 28, 29, 34, 36, 37, 43, 48, 49, 62, 63, 67, 72, 80, 82, 88, 92, 95, 165, 178 Meninges, 160, 178 Mental Disorders, 29, 34, 178, 186 Mental Health, iv, 23, 40, 139, 141, 178 Mental Processes, 166, 179, 186 Mental Retardation, 3, 5, 9, 16, 24, 27, 34, 35, 36, 40, 41, 45, 46, 64, 123, 125, 127, 145, 162, 179 Methylphenidate, 52, 179 Microbe, 179, 193 Microbiology, 154, 158, 179 Microorganism, 162, 179, 196 Microtubules, 11, 13, 179 Miscarriage, 130, 179 Mitochondria, 100, 101, 113, 119, 120, 179, 182
202
Williams Syndrome
Mitosis, 109, 157, 179 Modeling, 25, 40, 179 Molecule, 21, 100, 101, 102, 107, 156, 158, 162, 166, 172, 179, 181, 184, 187, 189, 195 Monitor, 179, 181 Monosomy, 9, 113, 156, 179 Morphological, 73, 167, 178, 179 Morphology, 49, 55, 68, 74, 76, 79, 86, 87, 179 Mosaicism, 10, 110, 179 Motility, 19, 179 Motion Perception, 29, 179 Muscle Fibers, 179, 180 Muscular Atrophy, 143, 180 Mutagens, 161, 170, 180 Mydriatic, 166, 180 Myocardial infarction, 70, 80, 164, 180 Myocardium, 180 Myotonic Dystrophy, 122, 143, 180, 194 N Narcolepsy, 165, 179, 180 NCI, 1, 138, 161, 180, 183 Necrosis, 157, 174, 180 Neonatal, 29, 54, 75, 180 Neoplasia, 143, 180 Nephropathy, 176, 180 Nervous System, 12, 122, 143, 160, 180, 191 Neural, 7, 27, 28, 29, 32, 39, 43, 44, 46, 47, 75, 180, 188 Neural Pathways, 47, 180 Neurologic, 5, 7, 76, 90, 147, 180 Neuronal, 25, 180 Neurons, 21, 25, 165, 170, 180, 191, 192, 195 Neuropathy, 24, 119, 180 Neurophysiology, 29, 30, 165, 180 Neurotransmitter, 154, 166, 180, 181, 189 Neutrophil, 21, 22, 23, 181 Nitrogen, 169, 176, 181 Nonverbal Communication, 162, 181 Norepinephrine, 155, 166, 181 Nuclear, 100, 158, 167, 168, 170, 175, 177, 180, 181, 186, 187, 192 Nuclear Envelope, 100, 181 Nuclear Pore, 181 Nuclei, 26, 155, 167, 168, 169, 171, 173, 175, 178, 179, 181, 186, 188, 195 Nucleic acid, 158, 164, 173, 174, 180, 181, 186, 188 Nucleic Acid Hybridization, 173, 181 Nucleosomes, 35, 45, 181
Nurse Practitioners, 128, 181 O Occipital Lobe, 32, 181, 195 Octamer, 45, 181 Oliguria, 176, 181 Oncogene, 143, 181 On-line, 71, 151, 182 Ophthalmology, 45, 169, 182 Optic Chiasm, 173, 182 Organelles, 99, 100, 164, 178, 182, 184 Otitis, 65, 182 Otitis Media, 65, 182 Ovaries, 127, 182, 189 Ovary, 19, 20, 74, 182, 191 Oxidative Phosphorylation, 101, 182 P Palliative, 182, 192 Pamidronate, 84, 182 Pancreas, 172, 175, 182 Pancreatic, 143, 182 Pancreatic cancer, 143, 182 Papilloma, 182, 187 Paradoxical, 56, 182 Paralysis, 51, 182 Parenteral, 167, 182 Parietal, 38, 42, 60, 156, 182 Parietal Lobe, 38, 156, 182 Paroxysmal, 143, 182 Patch, 61, 163, 182 Paternity, 127, 183 Pathologic, 157, 164, 183 Pathologic Processes, 157, 183 Pathophysiology, 29, 40, 46, 183 PDQ, 138, 183 Pelvic, 183, 185 Pelvis, 154, 182, 183, 194 Peptide, 183, 184, 185 Perception, 28, 29, 43, 46, 59, 64, 68, 69, 92, 172, 183 Perfusion, 27, 183 Perirhinal, 29, 183 Phallic, 169, 183 Pharmacologic, 156, 183, 193 Phenylalanine, 107, 183, 194 Phobias, 4, 183 Phospholipases, 183, 189 Phosphorus, 159, 183 Phosphorylation, 16, 17, 101, 183 Physical Examination, 125, 183 Physiologic, 155, 183, 187, 192 Physiology, 154, 180, 184 Pigment, 178, 184
Index 203
Pituitary Gland, 184, 188 Plants, 159, 171, 179, 181, 184, 193 Plaque, 156, 184 Plasma, 100, 156, 172, 176, 184, 188 Plasma cells, 156, 184 Plasticity, 25, 27, 39, 184 Plastids, 182, 184 Platelet Activation, 184, 189 Pneumonia, 163, 184 Point Mutation, 33, 184 Polycystic, 144, 184 Polymorphism, 129, 184 Polypeptide, 155, 173, 184, 196 Posterior, 26, 47, 155, 157, 160, 166, 168, 175, 181, 182, 184, 190 Postsynaptic, 184, 189 Potentiation, 184, 189 Practice Guidelines, 141, 184 Precursor, 166, 168, 181, 183, 185, 194 Prenatal, 39, 91, 127, 130, 152, 167, 171, 185 Presumptive, 37, 185 Prevalence, 40, 67, 80, 115, 185 Probe, 33, 36, 185 Progression, 29, 185 Progressive, 80, 113, 160, 161, 165, 176, 180, 184, 185 Prone, 35, 113, 122, 185 Prophase, 185, 191, 192 Prospective study, 177, 185 Prostate, 19, 20, 35, 143, 185 Proteolytic, 155, 162, 185 Protocol, 39, 43, 133, 185 Protons, 173, 185, 186 Proximal, 166, 186, 188 Pseudogenes, 23, 186 Psychiatric, 34, 59, 80, 162, 178, 186 Psychiatry, 34, 38, 49, 50, 60, 61, 63, 70, 90, 92, 169, 186 Psychic, 178, 186, 188 Psychology, 28, 29, 42, 43, 49, 50, 60, 61, 69, 70, 85, 90, 92, 94, 166, 186 Psychopathology, 40, 89, 186 Psychophysics, 28, 29, 186 Puberty, 52, 58, 65, 71, 80, 186 Public Policy, 140, 186 Pulmonary, 35, 50, 75, 77, 82, 85, 159, 161, 176, 186, 195 Pulmonary Artery, 35, 85, 159, 186, 195 Pulmonary Edema, 161, 176, 186 Pupil, 166, 180, 186 Purines, 158, 186 Pyrimidines, 158, 186
R Race, 175, 186 Radiation, 154, 168, 170, 175, 186, 187, 194, 196 Radiation therapy, 154, 175, 186 Radioactive, 173, 174, 175, 181, 186, 187 Reaction Time, 37, 39, 187 Reactive Oxygen Species, 21, 22, 187 Receptor, 17, 116, 154, 156, 166, 187, 189 Recombinant, 133, 187, 195 Recombination, 23, 31, 171, 187 Rectum, 156, 162, 166, 170, 176, 185, 187 Recurrence, 158, 187 Red Nucleus, 157, 187 Reentry, 54, 187 Refer, 1, 105, 109, 111, 116, 134, 159, 162, 169, 177, 187 Reflex, 59, 169, 187 Refraction, 187, 190 Remission, 158, 187 Reproductive cells, 112, 123, 124, 171, 172, 187 Research Support, 39, 187 Restless legs, 40, 187 Retinoblastoma, 19, 44, 115, 143, 187 Retinoblastoma Protein, 44, 187 Retroviral vector, 171, 188 Rhabdoid tumor, 35, 188 Ribonucleic acid, 107, 188 Ribose, 154, 188 Ribosome, 107, 188, 194 Robotics, 43, 188 S Salivary, 169, 182, 188 Scatter, 188, 194 Schizophrenia, 29, 120, 188 Sclerosis, 116, 143, 188 Screening, 14, 25, 27, 30, 34, 118, 127, 128, 130, 162, 171, 183, 188 Secretion, 176, 188, 195 Segmentation, 95, 188 Segregation, 187, 188 Seizures, 9, 182, 188 Sella, 79, 166, 184, 188 Sella Turcica, 79, 166, 184, 188 Semantics, 72, 188 Semen, 185, 188 Septal, 36, 156, 177, 188 Septal Nuclei, 156, 177, 188 Sequence Analysis, 54, 189 Sequencing, 135, 189, 192 Sex Characteristics, 154, 186, 189
204
Williams Syndrome
Sex Determination, 144, 189 Shock, 64, 189 Side effect, 134, 137, 155, 189, 191, 193 Signal Transduction, 31, 189 Signs and Symptoms, 4, 5, 12, 121, 122, 127, 187, 189 Skeletal, 9, 17, 18, 33, 189, 190 Skeleton, 154, 189 Skull, 189, 192 Small intestine, 173, 175, 189 Smooth muscle, 163, 189, 190 Sociability, 41, 189 Social Behavior, 42, 189 Social Perception, 41, 190 Social Work, 124, 190 Soft tissue, 159, 189, 190 Soma, 190 Somatic, 8, 110, 113, 124, 154, 177, 178, 179, 190 Somatic cells, 110, 113, 124, 178, 179, 190 Somatic mutations, 113, 190 Sound wave, 163, 190 Spasm, 72, 190 Specialist, 128, 148, 166, 190 Species, 22, 137, 168, 173, 175, 178, 179, 186, 187, 190, 191, 195 Spectrum, 14, 43, 46, 190 Sperm, 109, 110, 112, 113, 122, 123, 124, 127, 134, 161, 171, 172, 187, 190, 194 Sphenoid, 188, 190 Spinal cord, 157, 159, 160, 161, 178, 180, 187, 190 Sporadic, 187, 190 Stenosis, 4, 13, 14, 15, 31, 35, 36, 50, 55, 58, 63, 75, 82, 84, 85, 190, 191 Stent, 82, 190 Sterility, 174, 190 Stillbirth, 125, 190 Stimulant, 165, 179, 191 Stimulus, 29, 166, 176, 183, 186, 187, 191, 193 Stomach, 166, 168, 170, 173, 175, 189, 191 Stool, 162, 176, 191 Strand, 100, 191 Striate, 39, 191 Stricture, 190, 191 Stroke, 5, 39, 69, 70, 74, 118, 139, 160, 191 Stromal, 159, 191 Stromal Cells, 159, 191 Subacute, 174, 191 Subclinical, 58, 87, 174, 188, 191 Subiculum, 173, 191
Subspecies, 190, 191 Sudden death, 85, 191 Superoxide, 21, 191 Supportive care, 183, 191 Suppression, 34, 191 Sympathomimetic, 165, 166, 168, 181, 191 Symphysis, 161, 185, 191 Synapse, 155, 191, 192, 194 Synapsis, 191, 192 Synaptic, 25, 181, 189, 192 Synchrony, 50, 192 Synostosis, 81, 192 Syrinx, 86, 192 Systemic, 156, 159, 168, 174, 175, 187, 192 Systolic, 173, 192 T Telangiectasia, 144, 192 Telencephalon, 158, 160, 192 Telomere, 33, 192 Temperament, 42, 192 Temporal, 29, 32, 46, 155, 158, 169, 172, 173, 192 Temporal Lobe, 29, 155, 158, 192 Terminator, 162, 192 Thalamic, 157, 168, 192 Thalamic Diseases, 157, 192 Thalamus, 168, 177, 192 Therapeutics, 35, 192 Thermal, 166, 192 Third Ventricle, 168, 173, 192 Threshold, 173, 193 Thrombin, 185, 193 Thrombomodulin, 185, 193 Thrombosis, 185, 191, 193 Thyroid, 76, 86, 87, 127, 193, 194 Thyroid Gland, 127, 193 Thyroid Hormones, 193, 194 Tinnitus, 182, 193, 195 Tomography, 45, 193 Topical, 173, 193 Toxic, iv, 21, 99, 168, 180, 193 Toxicity, 133, 193 Toxicology, 140, 193 Toxins, 156, 174, 193 Trachea, 176, 193 Transcription Factors, 26, 31, 36, 37, 44, 108, 193 Transduction, 189, 193 Transfection, 158, 171, 193 Translation, 31, 107, 108, 171, 186, 194 Translocation, 8, 87, 161, 194 Transmitter, 157, 166, 181, 194
Index 205
Trinucleotide Repeat Expansion, 122, 194 Trinucleotide Repeats, 194 Trisomy, 9, 11, 113, 156, 194 Tuberous Sclerosis, 144, 194 Tubulin, 179, 194 Tumor suppressor gene, 11, 187, 194 Tyrosine, 16, 17, 166, 194 U Ultraviolet radiation, 110, 194 Uremia, 176, 194 Urethra, 185, 194 Urinary, 4, 67, 181, 194 Urine, 156, 159, 172, 176, 181, 194 Uterus, 127, 161, 164, 169, 170, 182, 194 V Vaccine, 185, 194 Vacuoles, 182, 195 Vascular, 14, 27, 35, 55, 82, 174, 193, 195 Vasodilator, 166, 195 Vector, 132, 133, 193, 195 Vein, 156, 181, 195 Venous, 185, 195 Venter, 11, 195 Ventral, 26, 37, 39, 42, 61, 173, 195 Ventricle, 155, 157, 173, 186, 192, 195 Ventricular, 192, 195 Venules, 159, 195
Vertigo, 182, 195 Vestibulocochlear Nerve, 173, 193, 195 Vestibulocochlear Nerve Diseases, 173, 193, 195 Veterinary Medicine, 140, 195 Viral, 132, 171, 193, 195 Virulence, 193, 195 Virus, 15, 132, 167, 184, 187, 188, 193, 195 Viscera, 190, 195 Visceral, 177, 195 Visual Cortex, 26, 28, 32, 39, 46, 195 Visual field, 179, 182, 196 Vitro, 127, 196 Vivo, 196 Vocal cord, 51, 89, 196 W White blood cell, 15, 110, 154, 156, 177, 181, 184, 196 Windpipe, 193, 196 Womb, 194, 196 X X-ray, 163, 170, 175, 181, 186, 196 Y Yeasts, 183, 196 Z Zygote, 163, 179, 196 Zymogen, 185, 196