Holoprosencephaly - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

HOLOPROSENCEPHALY

A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET

R EFERENCES

HOLOPROSENCEPHALY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

ii

ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 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., 1960Holoprosencephaly: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00548-4 1. Holoprosencephaly-Popular works. I. Title.

iii

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: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

iv

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 holoprosencephaly. 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.

v

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 Eli Lilly Chair Professor of Innovation, Business and Society 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.

vi

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. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

vii

Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON HOLOPROSENCEPHALY ............................................................................ 3 Overview........................................................................................................................................ 3 Federally Funded Research on Holoprosencephaly ........................................................................ 3 The National Library of Medicine: PubMed ................................................................................ 22 CHAPTER 2. NUTRITION AND HOLOPROSENCEPHALY .................................................................. 67 Overview...................................................................................................................................... 67 Finding Nutrition Studies on Holoprosencephaly ....................................................................... 67 Federal Resources on Nutrition ................................................................................................... 68 Additional Web Resources ........................................................................................................... 68 CHAPTER 3. ALTERNATIVE MEDICINE AND HOLOPROSENCEPHALY ............................................ 71 Overview...................................................................................................................................... 71 National Center for Complementary and Alternative Medicine.................................................. 71 Additional Web Resources ........................................................................................................... 72 General References ....................................................................................................................... 72 CHAPTER 4. BOOKS ON HOLOPROSENCEPHALY ............................................................................ 73 Overview...................................................................................................................................... 73 Book Summaries: Online Booksellers........................................................................................... 73 Chapters on Holoprosencephaly ................................................................................................... 73 CHAPTER 5. PERIODICALS AND NEWS ON HOLOPROSENCEPHALY ............................................... 75 Overview...................................................................................................................................... 75 News Services and Press Releases................................................................................................ 75 Academic Periodicals covering Holoprosencephaly ..................................................................... 77 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 81 Overview...................................................................................................................................... 81 NIH Guidelines............................................................................................................................ 81 NIH Databases............................................................................................................................. 83 Other Commercial Databases....................................................................................................... 85 APPENDIX B. PATIENT RESOURCES ................................................................................................. 87 Overview...................................................................................................................................... 87 Patient Guideline Sources............................................................................................................ 87 Associations and Holoprosencephaly ........................................................................................... 89 Finding Associations.................................................................................................................... 89 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 91 Overview...................................................................................................................................... 91 Preparation................................................................................................................................... 91 Finding a Local Medical Library.................................................................................................. 91 Medical Libraries in the U.S. and Canada ................................................................................... 91 ONLINE GLOSSARIES.................................................................................................................. 97 Online Dictionary Directories ..................................................................................................... 97 HOLOPROSENCEPHALY DICTIONARY ................................................................................. 99 INDEX .............................................................................................................................................. 131

1

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 holoprosencephaly 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 holoprosencephaly, 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 holoprosencephaly, from the essentials to the most advanced areas of research. 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 holoprosencephaly. 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 holoprosencephaly, 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. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on holoprosencephaly. The Editors

1

From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

3

CHAPTER 1. STUDIES ON HOLOPROSENCEPHALY Overview In this chapter, we will show you how to locate peer-reviewed references and studies on holoprosencephaly.

Federally Funded Research on Holoprosencephaly The U.S. Government supports a variety of research studies relating to holoprosencephaly. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) 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 holoprosencephaly. 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 holoprosencephaly. The following is typical of the type of information found when searching the CRISP database for holoprosencephaly: •

Project Title: CRANIOFACIAL DEFECTS IN ETHANOL-EXPOSED ZEBRAFISH Principal Investigator & Institution: Ahlgren, Sara C.; Assistant Professor, Pediatrics; None; California Institute of Technology Mail Code 201-15 Pasadena, Ca 91125 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2003 Summary: (provided by applicant): Craniofacial abnormalities are characteristic of embryonic exposure to alcohol. In typical fetal alcohol syndrome poor development of a

2

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).

4

Holoprosencephaly

number of facial features, all of which are derived from the cranial neural crest, is observed. This grant seeks to establish a zebrafish model to study the craniofacial defects associated with embryonic alcohol exposure, and to establish that such environmental insults produce craniofacial defects by interfering with normal signals that control growth. We will first establish what the optimal dose and time schedule for alcohol application is, with respect to deficits in cranial neural crest cells, taking into consideration doses which would be relevant to fetal alcohol syndrome. The zebrafish is an excellent model for comparing teratogens, like alcohol, with genetic defects, to determine what candidate genes might be altered by environmental conditions. In addition, it is possible to overexpress genes of interest by directed injection or transgenesis. The defects in fetal alcohol syndrome partially overlap with some features of holoprosencephaly, which is typically a more dramatic malformation of the central nervous system with associated midline facial features, arising from both genetic and environmental factors. One such genetic cause is a heterozygous mutation in the human Sonic Hedgehog gene. Partial inhibition of Sonic hedgehog in the chick embryo using function-blocking antibodies results in a phenotype similar to a mild holoprosencephaly that is intriguingly similar to fetal alcohol syndrome. The morphological similarity between embryos exposed to alcohol and partial inhibition of Sonic hedgehog suggests a potential mechanistic link. Zebrafish have multiple hedgehog genes, so it is possible that alcohol interferes with a common signaling pathway. To test the hypothesis that ethanol leads to cranial neural crest cell death via a decrease in the availability of zebrafish hedgehog genes, the experiments described in this grant will examine the effect of ethanol on the message levels of genes in the hedgehog signaling pathway. We will also examine the fate of cranial neural crest cells, as well as the growth of the craniofacial structures. We will further attempt to rescue the cranial neural crest cells after ethanol treatment by application of exogenous Sonic hedgehog. These experiments will lay the groundwork to expand our understanding of the mechanisms of craniofacial defects following embryonic exposure to alcohol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CYCLIC NUCLEOTIDES AND THE RESPONSE TO SONIC HEDGEHOG Principal Investigator & Institution: Roelink, Henk; Assistant Professor; Biological Structure; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 15-MAR-2002; Project End 31-JAN-2004 Summary: The Sonic Hedgehog is a signaling molecule that is required for normal development of the central nervous system. The response to Shh is complex, and can be changed by environmental compounds like cyclopamine. Changes in the Shh response result in a specific type of embryo malformations characterized by defects of the neural midline, like holoprosencephaly, which can be reflected in the face as cyclopia or hypotelorism. All cell types in the ventral neural tube develop as a consequence of Shh signaling, and it is likely that small changes in the Shh response has subtle effects on the formation of ventral cell types. This in turn might result in congenital neurological defects. It has been determined that the Shh response is influenced by the cyclic nucleotide concentration within the responding cells. Increasing the camp concentration attenuates the Shh response, while loss of the camp dependent kinase (PKA) activates the Shh response. These authors showed that increasing the cGMP concentration also enhances the response to Shh, suggesting a model in which the Shh response is dependent on the cyclic nucleotide concentration within the responsive cells, and that camp and cGMP have opposite effects on the Shh response. Several compounds present

Studies

5

in the environment can alter the intracellular cyclic nucleotide concentration, either by activating GTP/ATP cyclases, enzymes that generate cyclic nucleotides, or by blocking phosphodiesterases, enzymes that degrade cyclic nucleotides. It is hypothesized that environmental compounds that change the cyclic nucleotide complement of a cell, alter Shh response in such cells, resulting in embryo malformations and thus birth defects. The hypothesis will be tested using sensitive assays of the Shh response in the chick embryo. It will be determined if environmental compounds that change the cyclic nucleotide complement of a cell interfere with normal Shh signaling in the developing neural tube in vivo, or in neural explants in vitro. In humans, exposure to the compounds that will be tested is either voluntary, like forskolin, or involuntary, like bacterial enterotoxins, but in either case little is known about their possible adverse effects on early embryos and thus as a cause of birth defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FACTORS INFLUENCING SHH SIGNALING IN THE FOREBRAIN Principal Investigator & Institution: Kohtz, Jhumku D.; Children's Memorial Hospital (Chicago) Chicago, Il 606143394 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-APR-2008 Summary: (provided by applicant): The major purpose of this work is to investigate mechanisms governing brain development. Specifically, these studies focus on the signaling protein Shh, and novel proteins that regulate its activity. Many of the proteins in the Shh pathway have been shown to play an integral role in specific clinical disorders. Mutations in the Shh gene itself cause holoprosencephaly. The finding that Shh requires a C-terminal cholesterol moiety for signaling supports its involvement in limb, CNS, and facial malformations that result from genetic or environmentallyinduced cholesterol deficiency. From the proposed work on the mechanism of Shh Nterminal fatty-acylation, it is likely that mutation(s) of genes affecting the regulation of this process will also result in diseases similar to loss-of-function Shh mutants. In addition to developmental defects, mutations in patched or gli (genes in the Shh pathway) result in tumor formation. Thus, investigation of the mechanisms influencing Shh signaling will increase our understanding of a multitude of disease states that result from the disruption of this pathway. A major goal of these studies is to determine how specific forebrain neurons are generated. While it is known that grafting of fetal tissue into humans suffering from neurodegenerative disorders such as Huntington's and Parkinson's disease can be therapeutic, the lack of availability of donor tissue often limits this method. Given that both Huntington's and Parkinson's disease result from the degeneration of specific neuronal populations, the proposed work may reveal factors important to the regeneration of such neurons. Lastly, lessons learned from the use of replication-defective viruses and ultrasound-guided embryonic injections, as proposed in these studies, can be applied to perfecting tools for gene therapy, specifically to define the relationship between the timing and dose of exogenous agents in rescuing a particular disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: FUNCTION OF THE GLI GENES IN SONIC HEDGEHOG SIGNALING Principal Investigator & Institution: Ruiz I Altaba, Ariel Ruiz I.; Associate Professor; Cell Biology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2003; Project Start 20-FEB-1998; Project End 30-APR-2008

6

Holoprosencephaly

Summary: (provided by applicant): In this renewal project we propose to continue our research on the functions of the Sonic hedgehog (Shh)-Gli pathway in neural development during embryonic, perinatal and adult stages using the mouse as an experimental model. Specifically, we will study the role of Gli protein function in Nestin progenitors during mouse brain growth and patterning, focusing on their role in the neocortex. We will also investigate Shh-Gli function in neural stem cells, from both the embryonic neocortex and the postnatal and adult subventricular zone of the lateral ventricle. The results of our proposed research will help in understanding how this important signaling pathway regulates the growth and patterning of the brain, with special emphasis placed on the neocortex, a preeminent structure in human brain function. Our ongoing research on how progenitor cells respond to Shh-Gli function will help in understanding how the brain is formed, which will also lead to an understanding of the bases of a number of mental deficits. Indeed, our findings will likely shed light into the possible mental deficits that patients with viable forms of holoprosencephaly (a disease that can arise from defective SHH signaling) may display. In addition, the knowledge of how the SHH-GLI pathway affects brain precursors will help our understanding of how brain tumors arise, an area of research covered under a different, yet related, project in the laboratory. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: FUNCTION OF THE SIX AND EYA GENES IN RETINAL DEVELOPMENT Principal Investigator & Institution: Kumar, Justin P.; Biology; Indiana University Bloomington P.O. Box 1847 Bloomington, in 47402 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): One of the most exciting revelations in retinal biology is that the molecules and mechanisms that direct eye formation are conserved throughout the animal kingdom. In recent years an entire cascade of molecules and their roles in eye specification have been found to be preserved in both mammalian and invertebrate retinal systems. In addition to provoking a profound rethinking of the origins of the eye, the emerging commonality among mechanisms used in eye development allows for the use of model systems to provide insight into the development and diseases of the mammalian eye. The Sine oculis box (Six) and Eyes absent (Eya) gene families function within the signaling cascades that regulate eye and head development in both mammals and invertebrates. Bilateral anophthalmia and holoprosencephaly type 2 are caused by mutations within the human Six6 and Six3 genes, while molecular lesions within the human Eyal gene result in congenital cataracts, Branchio-Oto-Renal (BOR) and Oto-FaciaI-Cervial (OFC) syndromes. The association of Six and Eya gene lesions with eye diseases, provides us with an exciting opportunity to explore the roles played by the SIX and EYA proteins in retinogenesis. The developing eye of the fruit fly, Drosophila melanogaster, is an excellent experimental system for elucidating the genetic, molecular and biochemical mechanisms underlying the activities of the SIX and EYA proteins. In the fruit fly, the Six family is represented by the SINE OCULIS (SO) and OPTIX proteins, while the EYES ABSENT (EYA) protein is the only Eya family member. The goals of the proposed work are (1) to identify the steps in eye specification that are regulated by the Drosophila SIX and EYA family members; (2) to define the functional differences between the two fruit fly SIX proteins; (3) to understand the interactions of several signaling pathways with SO; and (4) to identify additional genes whose products participate in eye development and interact with SO. To achieve these goals, eye development will be analyzed in animals

Studies

7

lacking both SO and EYA proteins; biochemical approaches will be used to dissect functional differences between SO and OPTIX; and the well-established techniques of Drosophila genetics will be used to define relationships between SO and other key proteins involved in eye development. Together, these approaches will provide insight into the roles of the SIX and EYA proteins in eye specification. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENETIC ANALYSIS OF ROOF PLATE FUNCTION IN THE CNS Principal Investigator & Institution: Millen, Kathleen J.; Human Genetics; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 28-FEB-2009 Summary: (provided by applicant): We are studying dorsal CNS pattern formation in the mouse, as a paradigm for human congenital brain malformations based on the hypothesis that similar patterning defects underlie mouse and human malformations. Pattern formation is the term used to describe the emergence of spatial biological organization during development. Malformations of the dorsal midline of the human CNS are poorly understood congenital defects that include some forms of holoprosencephaly and megalencephaly. Both of these are primarily malformations of the dorsal cortex. An example of a dorsal midline malformation of the cerebellum is Dandy-Walker Malformation. The roof plate is a specialized dorsal midline structure in the embryonic CNS. It is a crucial regulator of dorsal patterning information in the developing spinal cord, directing the specification and differentiation of dorsal sensory interneurons via secreted molecules. We hypothesize that the roof plate performs a similar function in more anterior levels in the brain. Specifically, we hypothesize that the Lim-homeodomain encoding genes, Lmx 1a and Lmx 1b are required for normal roof plate development in the anterior CNS and that loss of these genes leads to loss of roof plate function and subsequent abnormal specification and differentiation of adjacent neurons in the developing cerebellum and cortex. We have previously demonstrated that the spontaneous neurological mouse mutant, dreher, harbors mutations in the Lmx 1a gene and that Lmx 1a is required for roof plate development in the mouse CNS. In the dreher spinal cord, no roof plate is generated. Consequently, the specification, patterning and differentiation of adjacent dorsal sensory interneurons are abnormal in the dreher spinal cord. At anterior levels of the developing CNS, a residual roof plate is still present in dreher mice, suggesting that roof plate in the brain has a different mechanism of genesis. This proposal makes use of gene targeting and transgenic technology in combination with extensive phenotypic analysis to examine the roles of Lmx 1a and the closely related gene, Lmx 1b, in roof plate formation and function adjacent to the developing cerebellum and cerebral cortex. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: GENETIC DEVELOPMENT

AND

MOLECULAR

ANLAYSIS

OF

NEURAL

Principal Investigator & Institution: Sirotkin, Howard I.; Neurobiology and Behavior; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2008 Summary: (provided by applicant): The diversity of cell types within the vertebrate nervous system depends on patterning events that occur at early stages of development. The specification and patterning of neural tissue is closely coupled to the development of the other germ layers. The mesoderm and endoderm are important sources of signals

8

Holoprosencephaly

that induce neural tissue and establish asymmetries within the neural plate. In this proposal, we seek to utilize the potent genetic and cellular methodologies available in the zebrafish to study patterning of the neural ectoderm. The zebrafish is well suited to this analysis. Zebrafish embryos are transparent and embryonic development occurs rapidly. These attributes foster detailed observation of normal and aberrant embryonic development. Zebrafish produce large numbers of offspring, which in addition to facilitating phenotypic characterization, enhances genetic analysis. The proposed experiments utilize several well characterized zebrafish mutations to investigate the molecular mechanisms that induce and pattern neural tissue. The general approach is to account for all the signals that generate anterior and posterior neural tissue. Models for both neural induction and patterning will be tested. A genetic screen is proposed to identify novel loci that disrupt anterior neural specification. The screen takes advantage of the ability to generate haploid zebrafish embryos in order to increases the throughput of the screen. There are two components to the screen: a morphology based approach to identify enhancers of a mutation (bozozok) which disrupts anterior neural patterning and an in situ based effort to detect alterations of the expression domains of the phox2a transcription factor. One promising mutation identified in a pilot screen alters anterior neural patterning and will be studied in detail. Because all vertebrates share fundamental similarities in the organization of their nervous systems, understanding the genetic networks that govern neural patterning in zebrafish will provide important insights into development of other species, including humans. Several zebrafish mutations have that disrupt embryonic development have anterior neural defects similar to a common human congenital abnormality, holoprosencephaly, and share similar etiologies. Deciphering the mechanisms of vertebrate axis formation may also provide insight into the causes other human developmental disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEDGEHOG DEVELOPMENT

SIGNAL

MODULATION

IN

MAMMALIAN

Principal Investigator & Institution: Chuang, Pao-Tien; Assistant Professor; Cardiovascular Research Inst; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (provided by applicant): The long-term goal of our studies is to elucidate the molecular mechanisms of cell-cell interactions during vertebrate development. This proposal focuses on the Hedgehog (Hh) signaling-pathway, which plays a key role in many developmental events. Mutations in members of the pathway are associated with the development of cancer, including basal cell carcinoma, the most prevalent cancer in Western countries, and a seemingly unrelated number of human syndromes and malformations, such as holoprosencephaly and polydactyly. Consequently, understanding how a Hh signal is received, transduced and modulated will be critical to understand how cells proliferate, differentiate or survive in response to the Hh signal, as well as how deregulated Hh signaling leads to diseases. These studies will also make it possible to perform prenatal genetic diagnosis and help design rational therapies for treating these Hh signaling-related diseases. Our general strategy is to focus on three membrane proteins, Hedgehog-interacting-protein (Hip), Patched (Ptch) and Smoothened (Smo), essential for transducing/modulating the Hh signal. The overall goals for this proposal are to define the role of Hip and Ptch in mammalian development through genetic analysis; to define the molecular interactions between Hip, Ptch and Smo in transducing/modulating Hh signal; and to identify missing

Studies

9

components in the Hh pathway. 1. To define Hip's role in Hedgehog signaling during mammalian development. A genetic approach utilizing transgenic knockout mice will be taken to dissect the distinct and overlapping roles Hip and Ptch play in modulating Hh signaling during mammalian development. 2. To elucidate the molecular interactions between the three known components of the Hh signaling pathway, Hip, Ptch and Smo, in transducing/modulating the Hh signal. Biochemical and cell culture approaches will be taken to investigate the molecular interactions between Hip, Ptch and Smo in transducing/modulating the Hh signal. 3. To use Hh-responsive cell lines, in combination with expression cloning and candidate gene strategies, to identify missing components in the Hh signaling pathway. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HEDGEHOG SIGNALING IN DROSOPHILA Principal Investigator & Institution: Kalderon, Daniel D.; Associate Professor; Biological Sciences; Columbia Univ New York Morningside 1210 Amsterdam Ave, Mc 2205 New York, Ny 10027 Timing: Fiscal Year 2002; Project Start 01-APR-1989; Project End 31-MAR-2006 Summary: Our objectives are to study the mechanisms of Hedgehog signal transduction in Drosophila and how Hedgehog signaling affects cell proliferation in the Drosophila ovary. Hedgehog family proteins are secreted molecules that instruct cell fate during development and can regulate cell proliferation even in adult organisms. These activities of Hedgehog (Hh) molecules are seen in many organisms from Drosophila, where Hh was first identified, to vertebrates including fish, frogs, mice and humans. In humans various defects in the Hh signaling pathway cause developmental abnormalities principally involving limbs, brain and facial structures (Holoprosencephaly, Grolin's syndrome, Greig's cephalopolysyndactyl, Pallister-Hall syndrome). In addition, a few specific cancers are associated with aberrantly activated Hh signaling pathway. Indeed, basal cell carcinoma, which is very widespread, is thought to be initiated exclusively by aberrant Hh signaling. The study of Hh signaling in Drosophila has brought many insights into the transduction process by which cells respond to a Hh signal and has also provided insight into how cells behaviors are altered by Hh signaling. The relative facility and sophistication of Genetic and Developmental analyses that are possible in Drosophila ensure that the pioneering role of such studies will continue. Subsequent studies have shown that most of the components and mechanisms of Hh signal transduction elucidated in Drosophila can also be demonstrated in vertebrate model organisms. In particular the role of Protein Kinase A (PKA) in silencing Hh signal transduction in the absence of a Hh signal is apparent in Drosophila and vertebrates. Our study of this role of PKA recently implicated additional protein kinases as regulators of Hh signaling. In this proposal we will define the role of these protein kinases and PKA in Hh signaling. We also found that Hh regulates proliferation in the Drosophila ovary by acting specifically on stem cells. We will define which other signaling pathways regulate these stem cells and how Hh alters their behavior. These studies are likely to be directly relevant to the behavior of human stem cells that give rise to hair follicles and epidermis and should help us to understand how basal cell carcinomas can originate from those stem cells or their derivatives. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: HEDGEHOG SIGNALING PATTERNS THE ZEBRAFISH PITUITARY Principal Investigator & Institution: Sbrogna, Jennifer L.; Biology; University of Massachusetts Amherst 408 Goodell Building Amherst, Ma 01003

10

Holoprosencephaly

Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): This proposal will examine the role of hedgehog (Hh) signaling in zebrafish pituitary development. The pituitary gland produces seven major hormones in vertebrates that influence vital physiological functions such as regulation of growth, reproductive function, and immune response. Defects in human pituitary development such as hypopituitarism affect a large number of children and are responsible for a variety of developmental problems including growth hormone deficiencies (GHD). Hypopituitarism is part of a number of syndromes (Holoprosencephaly, Pallister-Hall), that have been linked to defects in Hh signaling, a highly conserved signaling pathway. Using zebrafish genetics, we have shown Hh signaling is required for normal pituitary development. Our data shows Hh signaling influences zebrafish pituitary development during three phases: induction, patteming, and maintenance. The aims of this project are to use the accessible zebrafish embryo to construct a precise map defining different regional identities in the pituitary as they are forming, to characterize how defects in Hh signaling lead to different pituitary defects, and to understand when certain cell types need Hh signaling in order to differentiate as hormone secreting cells. The zebrafish Hh mutants provide a unique resource for dissecting the varied and critical roles Hh signaling plays in pituitary development. This work should relate directly to human developmental defects that affect the pituitary. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HOMEOBOX GENE SIX3 IN EYE DEVELOPMENT Principal Investigator & Institution: Oliver, Guillermo C.; Associate Member; St. Jude Children's Research Hospital Memphis, Tn 381052794 Timing: Fiscal Year 2002; Project Start 01-MAR-1998; Project End 30-JUN-2006 Summary: (provided by applicant): A few years ago, three novel murine homeobox genes (Six1, Six2, and Six3) closely related to the Drosophila sine oculis (so) gene were isolated; all are included in the Six/so gene family. Because of its early expression in the developing eye field, Six3 was initially thought to be the functional orthologue of the Drosophila so gene. This hypothesis was further supported by the demonstration that ectopic Six3 expression in medaka fish (Oryzias latipes) promotes the formation of ectopic lens and retina tissue, and by the finding that in humans, mutations in Six3 lead to holoprosencephaly. This grant application proposes a multidisciplinary approach to elucidate the functional and molecular events controlled by Six3, which will serve as an entry point to unravel some of the early steps leading to visual system development. A combination of functional genetics, molecular biology, and developmental biology studies has been designed to address important hypotheses in three specific aims. Morphologic and detailed molecular analyses will be performed to precisely characterize the phenotypes resulting from the targeted disruption of Six3 in mice, which was accomplished toward the end of the last granting period (Specific Aim 1). In addition, a conditional knock-out approach will be used to determine the tissue-specific roles of Six3 in each of the structures (lens, retina, and ventral forebrain) that normally express this gene (Specific Aim 1). The functional role, and the in vivo significance of the protein interactions that have been uncovered for Six3 during the last granting period will be characterized, and additional partners that interact with Six3 in vivo will be identified (Specific Aim 2). Finally, transgenic mice, in ovo electroporation, and results generated from microarray analysis will be used to identify other components of the Six3 regulatory pathway and to study the functional roles of some of these proteins in this process (Specific Aim 3). The proposed studies will generate new information concerning the mechanisms of Six3 function during early murine development and will

Studies

11

generate several useful animal models for the study of different aspects of visual system development and some pathological conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISM OF ACTION OF RETINAL DETERMINATION PROTEINS Principal Investigator & Institution: Hegde, Rashmi S.; Associate Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2004; Project Start 01-SEP-2004; Project End 31-AUG-2009 Summary: (provided by applicant): In recent years it has become apparent that the genetic networks specifying cell-fate are conserved across species. Interestingly, these regulatory cassettes are also deployed in multiple developmental contexts, for example in the morphogenesis of different organs. An excellent example of this is the Eyeless Eyes Absent - Sine oculis - Dachshund cascade originally described in fly eye development, and called the retinal determination pathway. An analogous pathway is involved in vertebrate eye and muscle development, and components of the network have been implicated in brain, ear, and kidney development. Mutations in these genes are associated with several human developmental diseases including bronchio-oto-renal syndrome and congenital cataracts (Eyes Absent), holoprosencephaly, bilateral anophtalmia and pituitary anomalies (mutations in the human sine oculis genes), aniridia (mutations in Pax6, the human homologoue of Eyeless), as well as postaxial polydactyly type A2, mental retardation, and a form of Bardet-Biedel syndrome (Dachshund mutations). It is our long-term goal to unravel the molecular mechanisms underlying these regulatory pathways. This proposal focuses on the two novel protein families in this network: Eyes Absent and Dachshund. We have recently obtained evidence that Eyes Absent has protein tyrosine phosphatase activity and that Dachshund contains a DNA-binding motif. These unexpected observations alter existing models for the roles of these two critical retinal determination proteins, and are the basis for the studies proposed here. We plan to use crystallography and biochemistry in an integrated effort to decipher the molecular mechanisms of Eyes Absent and Dachshund action during early embryonic development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: MICE THAT HOLOPROSENCEPHALY

LACK

CDO:

A

MODEL

FOR

MILD

Principal Investigator & Institution: Krauss, Robert S.; Associate Professor; Molecular, Cellular & Dev Biol; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): The objective of this high risk/high impact research proposal is to exploit the Cdo "knockout" mouse developed in this lab as a model for mild forms of holoprosencephaly (HPE), a human birth defect that affects craniofacial and forebrain development. Haploinsufficiency for Sonic hedgehog (Shh) is the most common known cause of both familial and sporadic HPE. The phenotype of Shh mutation carriers can be highly variable, even within a single pedigree, with craniofacial malformations ranging from cyclopia and a proboscis to absence of the nasal septum and a solitary median maxillary incisor. Although much is known about how Shh signals are transduced by target cells, few of the genes that this pathway regulates during craniofacial development have been identified. Cdo and Boc encode co-

12

Holoprosencephaly

components of a cell surface receptor that promotes differentiation of skeletal muscle precursor cells. Both genes are also expressed in developing facial structures affected in HPE. We have disrupted the Cdo gene in mouse ES cells and introduced this mutation into the germline. Mice lacking CDO display highly penetrant defects in craniofacial development that are strikingly similar to those observed in milder forms of HPE in humans, including lack of, or solitary central, maxillary incisors, and lack or hypoplasia of the cartilage of the nasal septum. A hypothesis based on a causal relationship between Shh signaling and Cdo and/or Boc expression is proposed for the development of facial anomalies in mild form HPE: Shh produced by the ectoderm of the developing frontonasal and maxillary processes induces the expression of Cdo and/or Boc in the adjacent mesenchyme. Subsequent activities of the CDO/BOC receptor are required for the determination, differentiation or survival of cells in this region, ultimately resulting in formation of specific midface structures. It is predicted that disruption of Shhmediated expression of Cdo and/or Boc results in facial anomalies characteristic of mild HPE. The specific aim of this proposal is to test this hypothesis with a combined embryological, genetic and cell biological approach. If the hypothesis is proven correct, the impact of this grant will be of great innovative value for the cell-signaling field and may lead to identification of molecular targets ultimately used for the diagnosis, prevention or treatment of mild HPE. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR ANALYSIS OF TRANSCRIPTIONAL REPRESSION BY TGIF Principal Investigator & Institution: Wotton, David; Center for Cell Signaling; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: (Adapted from the Investigator's Abstract): TGIF (TG-interacting factor) is a member of the TALE family of homeodomain proteins. TALE homeodomain proteins have a three amino acid insertion between helices one and two of the homeodomain, which specifies interactions with other DNA binding proteins. In humans, mutation of TGIF leads to holoprosencephaly, a genetic disorder resulting in profound effects on craniofacial development. TGIF is a transcriptional repressor, which acts in part by recruiting histone deacetylases, and is a transcriptional co-repressor for TGF-betaactivated Smads. In response to TGF-beta, an activated Smad complex enters the nucleus, binds to DNA and interacts either with transcriptional activators, or a corepressor complex via TGIF. It appears that TGIF acts in distinct transcriptional regulatory pathways: Repressing transcription of TGF-beta-activated genes via Smads and repressing a second set of genes when bound directly to DNA. However, target genes, regulated by direct binding of TGIF are not known. The goal of this project is to understand the mechanism of action of TGIF and its role in transcriptional regulation. Specifically, this project will analyze transcriptional repression by TGIF at the molecular level, and determine and its role in TGF-beta-activated transcription. Target genes for TGIF, and DNA binding proteins, with which TGIF interacts, will be identified. These studies will help us understand how defects in TGIF lead to holoprosencephaly, and shed light on TGF-beta-activated transcriptional regulation, which when perturbed by mutations affecting Smad proteins, contributes to cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

Studies

•

13

Project Title: MOLECULAR GENETICS OF FOREBRAIN DEVELOPMENT Principal Investigator & Institution: Schier, Alexander F.; Associate Professor; Cell Biology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 17-APR-2000; Project End 31-MAR-2004 Summary: The long-range goal of this project is to dissect the hedgehog signaling pathway and determine its role in forebrain development. Our studies focus on the genetic and molecular basis for the formation of the ventral diencephalon and the associated anterior pituitary. We have identified four zebrafish mutations that affect the development of this embryonic region: sonic you, detour, you-too, and chameleon. The sonic you mutation disrupts the zebrafish sonic hedgehog gene, and our recent studies have identified detour and you-too as mutations in zebrafish gli1 and gli2, respectively. Members of the gli gene family encode transcription factors that are thought to mediate hedgehog signaling. The finding that three of the four diencephalic genes affect components of the hedgehog signaling pathway establishes the important role of this universal signaling cascade during forebrain development. We propose to further determine the function and regulatory interactions of the hedgehog signaling pathway during the development of ventral diencephalon and anterior pituitary by A) conducting a detailed analysis of diencephalic and pituitary development in wild-type and sonic you mutant embryos using marker gene expression and fate map analysis; B) studying the transcriptional and post-translational regulation of gli factor activity by hedgehog signaling; C) cloning the chameleon gene. Abnormal diencephalic and pituitary development has been implicated in human congenital disorders such as holoprosencephaly, and components of the hedgehog signaling pathway are involved in human cancer. The proposed studies will thus help to provide the necessary context for understanding birth defects and cancer formation in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: FUNCTION

MOLECULAR

MECHANISMS

OF

HEDGEHOG

RECEPTOR

Principal Investigator & Institution: Beachy, Philip A.; Molecular Biology and Genetics; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-JUN-2005 Summary: (appended verbatim from investigator's abstract): Holoprosencephaly (HPE) a defect in developmental patterning of the face and forebrain is the most common malformation in early human pregnancy with an incidence of 1/250 during the first trimester. Basal cell carcinoma (BCC) is the most common form of cancer in Caucasians with 750,000 cases treated annually in the United States alone. Both conditions are associated with inappropriate activity of the Hedgehog (Hh) signaling pathway, a deficit during the embryonic period in the case of HPE and excess postnatal activity in the case of BCC. This proposal centers on the mechanisms by which the Hedgehog extracellular protein signal is sensed and transmitted to intracellular components and on the mechanisms by which a localized source of Hedgehog signal elicits a graded pattern of pathway activity in cells of a developing tissue. The Hedgehog receptor comprises two polytopic transmembrane proteins Patched (Ptc) and Smoothened (Smo) with twelve and seven transmembrane spans respectively. Genetic evidence suggests that Ptc suppresses the activity of Smo and that Hh binding to Ptc relieves this suppression allowing for activation of downstream targets. Although Smo is related to the Frizzled family of Wnt receptors and more distantly to members of the Gprotein coupled receptor family, other components of the Hh pathway have no counterparts in other

14

Holoprosencephaly

signaling pathways. Molecular mechanisms of Hh receptor action thus remain unknown and experimental observations are not adequately explained by current models. We have recently developed several novel tools including various purified protein and antibody reagents a series of specific Hh receptor inhibitors sensitive cultured cell signaling assays and methods for selecting cells with high or low levels of Hh pathway activity. Using these tools together with a broadlybased experimental approach that incorporates pharmacological biochemical molecular and cell biological methods we propose: (1) to determine how components of the Hh receptor transduce the signal across the membrane; 2) to determine how Hh receptor activation affects intracellular components; and 3) to understand how a localized Hh signal elicits a graded pattern of pathway activity from cells within developing tissues such as the limb bud or neural tube. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MORPHOGENESIS AND PATTERNING OF CRANIOFACIAL PRIMORDIA Principal Investigator & Institution: Helms, Jill A.; Associate Professor; Orthopaedic Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-JAN-1998; Project End 31-DEC-2003 Summary: (Adapted from investigator's Abstract): The overall goal of this research proposal is to characterize the roles of two signaling molecules, sonic hedgehog (shh) and retinoic acid, in craniofacial development. Mutations in the SHH locus are associated with craniofacial defects such as holoprosencephaly, and embryos with deletions in retinoid receptors exhibit craniofacial malformations. Abundant molecular evidence also demonstrates that SHH and retinoid signaling are required in the early stages of craniofacial development, when the neural plate and neural ridge are patterned. However, the contribution of SHH and retinoid signaling to later stages of development, when the craniofacial primordia are patterned, is unknown. Recently epithelial domains in the embryonic face were identified that express shh and exhibit polarizing activity in a functional assay. Retinoic acid is required for the establishment of the limb organizer, and recent evidence from the applicant suggests a similar role in the face. It is hypothesized that retinoid signaling is required to establish organizing centers in the face, and that organizing activity mediated by SHH participates in craniofacial outgrowth and patterning. Two specific aims are proposed to test this hypothesis. First, gain-of-function and loss-of-function experiments will be used to characterize the role of organizing tissues and SHH function in the craniofacial primordia. This will be achieved by creating ectopic sites of polarizing activity through interspecific transplantations and retrovirally expressed SHH protein. Organizer function will be inhibited through surgical removal and through the use of antibodies that block the function of SHH. In both cases embryos will be evaluated for variations in gene expression and changes in skeletal and soft tissue morphology. Second, biochemical and genetic approaches will be used to test whether retinoids are required to establish organizing centers and induce shh expression in craniofacial primordia. A transient blockade in retinoid signaling will be created using pan-specific retinoid receptor antagonists, and the effect on gene expression and morphology will be studied. Whether the craniofacial malformation in Small-eye mice, caused by a loss of retinoic acid-producing mesenchymal cells in the frontonasal process, is associated with disruptions in organizing activity and shh expression will be determined. Collectively,

Studies

15

these experiments will determine the contributions of two important signaling molecules in normal and abnormal development of the embryonic face. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATTERNING OF THE OPTIC VESICLE BY EXTRINSIC FACTORS Principal Investigator & Institution: Fuhrmann, Sabine; Ophthalmology and Visual Scis; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2004 Summary: (provided by applicant): The long-term goal of this project is to understand how cellular and tissue-tissue interactions regulate development of the central nervous system. Disruption of tissue-tissue interactions can lead to a wide range of serious birth defects affecting the brain and eye, such as holoprosencephaly, congenital anophthalmia, microphthalmia, and anencephaly. Understanding the normal process of development will allow for better prevention and treatment of such defects. It is proposed to study the role of signaling molecules involved in these interactions using the embryonic eye as a model system for forebrain development, where the same mechanisms most likely regulate regional specification. Classical embryological studies have shown that the extraocular tissues are required for normal eye growth and differentiation. At present there is little information about the signals involved in these interactions. In explant cultures of optic vesicles from chick embryos, removal of the extraocular mesenchyme severely interferes with the formation of the retinal pigmented epithelium (RPE). The TGFbeta family member activin has been shown to be a candidate signal that exactly mimics the effects of the extraocular mesenchyme on RPE development in vitro. It is proposed to test the hypothesis whether the activin signaling pathway is required for RPE formation in the chick embryonic eye (Aim 1). To interfere with the activin signaling pathway in the developing RPE, soluble activin type II receptors will be applied as well as ectopic expression of antagonistic Smads (Smad6, 7) and truncated activin type II receptors using electroporation. It will be determined whether activin or a related signal is produced by the extraocular mesenchyme (Aim 2). Since cranial mesenchyme contains the inducer of RPE development, sufficient amounts of this tissue can be isolated for a degenerate PCR strategy. Subsequently, the identified molecule will be cloned and tested for the RPE-promoting activity in explant cultures and by transfection of chick embryos. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: PATTERNING THE DEVELOPING BRAIN Principal Investigator & Institution: Ming, Jeffrey E.; Investigator; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 191044399 Timing: Fiscal Year 2002; Project Start 07-JUL-1998; Project End 30-JUN-2003 Summary: Development of the brain is extraordinarily complex and requires the precise coordination of both cellular and molecular processes. The establishment of dorsalventral and rostral-caudal axes is an essential step in early brain formation. Disturbances in this process can result in Mental retardation and brain malformations. In fact, holoprosencephaly (HPE), a severe brain anomaly, can arise from abnormalities in genes regulating dorsal-ventral patterning. Haploinsufficiency for Sonic Hedgehog (Shh), a secreted factor which induces ventral identity of the brain, causes HPE in humans. In addition, overexpression of bone morphogenetic protein 5 (BMP5), a dorsal brain inducer, also results in HPE. These data indicate that HPE arises from aberrant dorsal-ventral specification. This proposal seeks to examine the mechanisms that

16

Holoprosencephaly

determine dorsal- ventral axis formation in the, vertebrate forebrain and their relationship to the pathogenesis of human brain malformations. Since loss ot expression of Shh and ectopic expression of BMP5 both result in HPE, we hypothesize that mutations affecting other genes in these pathways will also disrupt normal patterning and lead to HPE. We will test this hypothesis in two ways. First, the mechanisms of BMP5 action in the forebrain will be examined by studying the function of BMP receptors (BMPRs) in the chick embryo, an established model of brain development. Constitutively active and dominant negative BMPR constructs will be expressed in the chick brain and the resulting morphologic, cellular, and genetic consequences will be analyzed. Second, since mutations in Shh are detected in only a fraction of HPE cases, mutation screening of several genes in the Shh and BMP pathways in individuals with HPE will be conducted. This proposal describes a five-year training program in which the applicant will acquire the skills and experience required of an independent physician scientist. The primary focus throughout the grant period will be laboratory benchwork, complemented by coursework, journal clubs, and limited clinical responsibilities relevant to the project. The expertise of the mentors will provide broad and in-depth training in two areas: an animal experimental model of development, and analysis of human genes. The proposed studies will enable the candidate to transition into an independent investigator capable of integrating mutation analysis, functional developmental studies, and clinical diagnosis in future studies of the molecular basis of development and human genetic diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF CNS AND LIMB POLARITY BY SONIC HEDGEHOG Principal Investigator & Institution: Mcmahon, Andrew P.; Professor; Molecular and Cellular Biology; Harvard University Holyoke Center 727 Cambridge, Ma 02138 Timing: Fiscal Year 2002; Project Start 01-DEC-1994; Project End 30-NOV-2004 Summary: (adapted from investigator's abstract): The goal of this project is to understand the mechanisms by which information encoded in extracellular signals is converted complex patterns in the developing mammalian embryo. This proposal focuses on the role of Sonic hedgehog (Shh) signaling. The Shh signaling pathway is not only essential for the induction of clinically relevant neurons within the CNS, but inappropriate activation of Shh signaling has been linked to the development of several l of tumor, most notably basal cell carcinoma (BCC), the most common form of skin cancer, and medullablastoma, the most common brain tumor of children. Further, loss of Shh signaling underlies many cases of familial an spontaneous holoprosencephaly. Consequently, understanding how a Shh signal is received, transduced and modulated is likely to lead to new insights with direct relevance to human health. In view of its close relation. to the human embryo, and the availability of genetic approaches which can precisely modify gene activity, the mouse is used as an experimental system. An active Shh signal is generated by an unusual autocatalytic cleavage which leads to the covalent attachment of cholesterol to the l9 kcal signaling peptide. Cholesterol modification may play several roles in Shh-signaling, for example preventing free diffusion of ligand or participating in receptor recognition. Aim 1 proposes to explore the biological significance of cholesterol modification by generating a non-tethered allele of Shh (N-Shh). The activity of this allele in CNS and limb patterning will be addressed in the presence of normal or reduced levels of two Hedgehog binding proteins, Hip and Ptc, negative modulators of Shh signaling. Aim 2 proposes to characterize the Shh interaction domain of Hip using truncated forms of Hip produced by cultured cells, or

Studies

17

by limited proteolysis of purified Hip. Hip's role in embryogenesis and its genetic interactions with Ptc-l, will be examined in mice carrying Hip and Ptc null mutations. A mouse strain (Shh') has been generated in which an essential exon of Shh is flanked by the target recognition sequences (loxP sites) of the P1 phage integrase, CRE. Intercrossing the conditional allele with transgenic lines express CRE allows the spatial and temporal removal of Shh function. Aim 3 proposes to adopt this strategy to address Shh action in the limb and specific regions of the developing CNS, where its role cannot be assessed with existing null mutations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF GEMININ EXPRESSION IN EMBRYONIC ECTODERM Principal Investigator & Institution: Kroll, Kristen L.; Molecular Biol & Pharmacology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Our long-term objective is to dissect the molecular circuitry that underlies cell fate determination in the neurectoderm during early vertebrate embryogenesis. Information obtained in these studies may ultimately impact multiple human health issues, including our ability to manipulate embryonic stem cells for human therapies in the nervous system, and our understanding of the molecular basis of birth defects, including holoprosencephaly and spina bifida. These birth defects are among the most common congenital malformations in humans. Our general strategy is to focus upon a group of genes that act as primary effectors of neural fate during early embryogenesis. Expression of these genes in the future neural plate represents the earliest transcriptional response of ectoderm to neural-inducing signals from adjacent cells. This expression demarcates the embryonic ectoderm into neural versus non-neural territories. It is not known how this transcription arises or which molecular determinants and signaling pathways are direct regulators. Here, we have used a manipulatable transgenic Xenopus embryo system to reconstitute cis-regulatory controls underlying the early neural expression of one such gene, geminin. We show that 5' regulatory sequences from geminin recapitulate its expression and respond to inductive signals in the same manner as the endogenous gene. We propose use of several approaches to identify discrete cis-elements and protein complexes that directly control the onset of geminin's initial neural-specific transcriptional program, including injection and transgenic methodologies in vivo and various molecular methodologies in vitro. These studies should fill a critical gap in our understanding of the molecular basis of neural cell fate determination. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: REGULATION PROLIFERATION

OF

GI

&

NEURAL

EPITHELIAL

CELL

Principal Investigator & Institution: Mishra, Bibhuti B.; Associate Professor; Medicine; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (Adapted from the Applicant's Abstract): SMAD proteins are intracellular signaling molecules of TGF-beta and have been shown to play a pivotal role in gastrointestinal carcinogenesis. The applicant's group has recently reported a novel phenotype with heterozygous Smad 2/3 knockout intercrosses, with all mutants dying at E14 with marked liver hypoplasia and holoprosencephaly. The Smad 2/3 mutants

18

Holoprosencephaly

were notable for a marked fall in the expression of ELF 3, a beta-spectrin previously cloned by the applicant's group. Antisense studies suggest a crucial role for ELF 3 in biliary epithelial cell formation. In addition, Smad 2 and Smad 3 bind to ELF3. Experiments in this proposal are aimed at testing the hypothesis that ELF 3 plays a pivotal role in TGF-beta signaling involving both gastrointestinal and anterior cranial development. The specific aims are: 1. (i) To determine the phenotypic and molecular basis of the size heterogeneity of ELF proteins, and (ii) to test whether ELF can associate with other signal transducing proteins to gain an understanding of the mechanism of action of ELF. 2. (i) To characterize the interaction of ELF with Smads and to define the domains in Smads that bind ELF, (ii) to confirm interaction of ELF and Smads by coimmunoprecipitation experiments, and (iii) to investigate whether TGF-beta receptormediated phosphorylation of Smads or ELF may regulate their interaction. 3. To study the functional importance of ELF in TGF-beta signaling by defining the domains in ELF that interact with Smad 2, its subcellular localization, and its association with the TGFbeta receptor. 4. To determine whether ELF regulates the subcellular localization of Smad 2 and Smad 3 based on the preliminary evidence suggesting that ELF functions upstream of the Smad signaling pathway. These studies should lead to a greater understanding of the specific role Smad 2, Smad 3, and cytoskeletal proteins such as ELF in both gastrointestinal and anterior cranial development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF NODAL SIGNALING IN HOLOPROSENCEPHALY Principal Investigator & Institution: Ding, Jixiang; Mol/Cell/Craniofacial Biology; University of Louisville Jouett Hall, Belknap Campus Louisville, Ky 40292 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 30-JUN-2009 Summary: (provided by applicant): Holoprosencephaly represents a common birth defect (1:16,000 in live births and 1:250 in stillbirths) with a broad spectrum of craniofacial malformations ranging from distressful cyclopia to mild symptom of a single central incisor. It is caused by defects in the specification of the ventral forebrain (a part of the anterior axial midline), which subsequently lead to incomplete separation of the brain into the left and right hemispheres. Recent studies indicated that Nodal signaling plays a central role in controlling midline development, we therefore will focus on the regulation of Nodal signaling in mouse embryogenesis with a special interest in anterior axial midline formation. Nodal is a member of the transforming growth factor beta (TGF-beta) superfamily that utilizes a signaling pathway defined by Activin type I and II receptors, Smad2 and 4, and FoxH1 (FAST). Importantly, members of the EGF-CFC family of extracellular proteins such as mouse Cripto are essential cofactors for Nodal. We previously reported a Cripto Null allele, and recently we generated a Cripto hypomorphic allele, Cripto3-loxP, by genetic manipulation. Approximately 50 percent of the Cripto3-loxP/CriptoNull mice displayed a wide range of axial midline defects resembling holoprosencephaly. In contrast, TGIF is a homeobox gene encoding a nuclear protein that antagonizes TGF-( signaling by blocking Smad2 function. Interestingly, mutations in human TGIF gene are associated with holoprosencephaly, suggesting its function in axial midline formation, presumably through regulating Nodal/Smad2 signaling pathway. Based on these results, we will pursue the following Specific Aims in the proposed research: I) Analysis of the Cripto3loxP/CriptoNull mice as a model system for ventral forebrain defects and HPE by detailed analysis of the defects in Cripto3-loxP/CriptoNull mice at morphology and molecular levels; II) Investigation of mechanisms underlying Cripto function in mouse axial midline formation by identifying the tissues and cells where Cripto is functioning

Studies

19

and downstream target genes of Cripto; III) Investigation of TGIF function in mouse axial midline development by generating TGIF null embryos and examining the modulation of Nodal signaling by TGIF. These studies should improve our understanding of mammalian axial midline formation and human holoprosencephaly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ROLE OF THE ZIC2 GENE IN CNS DEVELOPMENT & MALFORMATION Principal Investigator & Institution: Brown, Stephen A.; Obstetrics and Gynecology; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 15-DEC-2001; Project End 30-NOV-2005 Summary: Holoprosencephaly (HPE) is a severe brain malformation in which midline structures fail to form during early development. We have recently demonstrated that heterozygous mutations (haploinsufficiency) of the transcription factor gene, ZIC2 cause HPE in humans, and our studies with transgenic mice also demonstrate that alterations in the pattern and/or level of Zic2 expression result in a variety of malformations such as exencephaly, anencephaly and facial hypoplasia. These results indicate that Zic2 has a critical role in CNS and facial development. Although evidence suggests that Zic2 acts early in development and may regulate the size of certain populations of cells in the dorsal neural tube, neural crest and somites, little is known about how the Zic genes, including Zic2, function at a cellular or molecular level. The long term goal of our research is to develop a detailed understanding of how altered ZIC2 expression results in human brain malformation. Experiments in this proposal are designed to elucidate Zic2 function in development by: 1) Examining the morphologic and molecular effects of Zic2 over-expression in a transgenic mouse model; 2) Determining the cellular and molecular effects of Zic2 mis-expression in the chick neural tube; 3) Determining potential upstream regulators of Zic2 expression; and 4) Exploring the protein-protein interactions that are essential for normal Zic2 function. When completed, the studies we propose will fill in many of the gaps in our present understanding of the role of Zic2 and how it interacts with other developmental pathways. In addition, our studies will elucidate the cellular and molecular processes that result in HPE and will therefore be useful in understanding this and other brain malformations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: SIGNALING CELL SPECIFICATION FOREBRAIN Principal Investigator & Institution: Karlstrom, Rolf O.; Assistant Professor; Biology; University of Massachusetts Amherst 408 Goodell Building Amherst, Ma 01003 Timing: Fiscal Year 2002; Project Start 01-JUL-2000; Project End 30-JUN-2004 Summary: (Applicant's abstract reproduced verbatim): The hedgehog (Hh) family of secreted proteins plays a fundamental role in cell differentiation within the brain, spinal cord, limbs, somites and circulatory system. Defects in Hh signaling during embryonic development are associated with human congenital malformations, including holoprosencephaly. Mis-regulation of Hh signaling later in life is associated with basal cell carcinoma, the most common form of cancer affecting fair-skinned adults. The study of Hh signaling during development is thus important for understanding human congenital malformations as well as the formation of certain tumors. The major goal of this project is to understand how Hh signaling contributes to cell differentiation during normal development in the zebrafish embryo. We have used a genetic approach to study the role of Hh signaling in the formation of a defined region of the nervous

20

Holoprosencephaly

system, the post optic area of the ventral forebrain. We have recently shown that two zebrafish forebrain mutations encode Hh-responsive transcription factors of the gli family. Cell differentiation defects in the zebrafish forebrain mutants appear to be caused by mis-regulation of Hh signaling. Consistently, it was also recently demonstrated that another zebrafish forebrain mutation encodes sonic hedgehog. The fact that three of the zebrafish forebrain mutants encode members of the Hh pathway underscores the importance of this signaling cascade in development. This application focuses on a fourth zebrafish forebrain mutant called umleitung (uml). Like the known Hh pathway mutations, uml interferes with Hh signaling and cell differentiation in the ventral forebrain. We now have evidence that uml may encode another zebrafish gli gene. While gli genes appear to be central to the regulation of Hh signaling, little is known about how gli genes function in vertebrates. There is evidence that some gli genes activate the transcription of Hh target genes, while others act to repress Hh targets. We propose to analyze the role of gli mediated hedgehog signaling in zebrafish forebrain development by A) identifying the gene encoded by uml, determining the genetic lesion in uml, and isolating null alleles of uml, B) determining how gli genes contribute to cell differentiation in the ventral forebrain, C) determining how gli genes regulate, and in turn are regulated by, Hh signaling in vivo, and D) identifying and characterizing genes that are transcriptionally regulated by gli genes in the zebrafish embryo. The zebrafish embryo provides a powerful model for the study of Hh regulation in vertebrates as it allows a genetic approach to be combined with ectopic expression studies. The combination of these two approaches is well suited to the study of molecular signaling pathways that regulate cell fate decisions and promises to provide insights not readily attainable in other vertebrate systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE ROLE OF MEGALIN IN CRANIOFACIAL DEVELOPMENT Principal Investigator & Institution: Argraves, W Scott.; Associate Professor; Cell Biology and Anatomy; Medical University of South Carolina P O Box 250854 Charleston, Sc 29425 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Craniofacial malformations, including a range of forebrain defects collectively known as holoprosencephaly (HPE), are the most common birth defects that occur in humans. The variation in the characteristics defining HPE suggests that multiple genes contribute to the syndrome. Mutation of the gene for sonic hedgehog (Shh), a signaling protein known for its crucial role in patterning tissues, including structures of the face, brain, spinal cord and eye has been shown to cause HPE. A HPE phenotype has also been described in mice that are deficient in the expression of megalin, an endocytic receptor related to the LDL receptor. Our studies have revealed previously unknown relationships between megalin, Shh and the Shh receptor, patched-1 (Ptc-1). These include the findings that megalin binds Shh and mediates its endocytosis and that megalin also influences subcellular trafficking and proteolytic processing of Ptc-l. W8 therefore hypothesize that megalin activity is an integral part of the mechanism by which Shh acts to control craniofacial morphogenesis. To test this hypothesis, experimentation is proposed to investigate megalin-mediated intracellular trafficking of Shh. Our results indicate that megalin-internalized Shh bypasses lysosomes. Given the fact that megalin is known to mediate transcytosis of several ligands; a major emphasis is to determine if megalin mediates transepithelial transport (transcytosis) of Shh. Such transcytosis would represent a novel mechanism to explain long range Shh signaling during development. Experimentation will also focus

Studies

21

on establishing the relationship between megalin and Ptc-1, including characterization of the role of megalin in regulating targeting of Ptc-1 to lysosomes and proteolytic processing of Ptc-l. Proteolytic processing of Ptc-1 is a new observation that is made more interesting by our finding that a carboxy-terminal fragment of Ptc-1 is translocated to the nucleolus, suggestive of a role in regulation of gene expression. Additional experimentation is directed towards establishing the role of megalin in regulating Shhdependent gene expression important for eye development and neuron specification. The proposed experimentation is expected to lead to new insights into the mechanism by which Shh signaling controls craniofacial development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SIGNALING

TRANSCRIPTIONAL

CONTROL

OF

SONIC

HEDGEHOG

Principal Investigator & Institution: Epstein, Douglas J.; Assistant Professor; Genetics; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-MAR-2000; Project End 28-FEB-2005 Summary: Deciphering the genetic pathways involved in fundamental aspects of mouse development has contributed significantly towards our understanding of the causes of human congenital abnormalities and tumor formation. The secreted protein Sonic hedgehog (Shh) is a requisite component of one such signaling pathway required to establish patterns of cellular growth and differentiation in many tissues during embryonic development. Within the central nervous system (CNS), Shh is essential for the specification of diverse neuronal cell fates deriving from the ventral portion of the neural tube including, spinal motor neurons, hindbrain serotonergic neurons and midbrain dopaminergic neurons. For Shh to carry out its role as an inductive signal it must be expressed in the correct tissues, at the proper developmental stage, as well as in the appropriate concentration. In humans, the developing ventral forebrain is particularly sensitive to the level of Shh expression given that a 50 percent reduction in the normal dosage causes holoprosencephaly, a structural defect of the brain resulting from the failure to form a ventral midline. In contrast, over-activation of the Shh signaling pathway has been implicated in the generation of several tumors, including medulloblastomas and basal cell carcinomas. These findings indicate that the Shh pathway must be kept under tight regulatory control during pre- and postnatal stages. Studies in Drosophila have identified many of the components implicated in regulating transduction of the pathway downstream of the Hedgehog (Hh) signal and have been shown to function in similar ways during vertebrate development. Little, however is known of the transcriptional requirements functioning to activate Shh at its sites of embryonic expression. The experiments outlined in this proposal are aimed at identifying the genes that regulate Shh transcription in the axial mesoderm and ventral midline of the neural tube, two signaling centers from where Shh has been shown to exert its inductive influences on ventral CNS differentiation. A mixture of standard and novel reporter assays carried out in transgenic mice will be used to ascertain the identity of the cis-acting regulatory sequences and the factors that bind to them, functioning to coordinate Shh transcription in the embryo. Multiple genes operating in a combinatorial manner have been predicted to regulate Shh in a regionalized manner within the CNS. An understanding of how Shh expression is initiated in the ventral forebrain may provide insight into additional causes of holoprosencephaly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

22

Holoprosencephaly

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.3 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 holoprosencephaly, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “holoprosencephaly” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for holoprosencephaly (hyperlinks lead to article summaries): •

A case of cebocephaly-holoprosencephaly with an aberrant adenohypophysis. Author(s): Ikeda H, Niizuma H, Suzuki J, Takabayashi T, Ozawa N. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1987; 3(4): 251-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3319140

•

A case of false median cleft of upper lip with IV-A holoprosencephaly that underwent cheiloplasty at 2.5 years of age. Author(s): Kobayashi J, Arai N, Kiyosaki I, Uzawa N, Ishii J, Yoshimasu H, Amagasa T. Source: Oral Diseases. 2000 November; 6(6): 391-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11355272

•

A case of holoprosencephaly. Author(s): Hou HD. Source: Chinese Medical Journal. 1987 October; 100(10): 816-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3127135

•

A case of suspected teratogenic holoprosencephaly. Author(s): Stabile M, Bianco A, Iannuzzi S, Buonocore MC, Ventruto V. Source: Journal of Medical Genetics. 1985 April; 22(2): 147-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3989833

3

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.

Studies

23

•

A gene for autosomal dominant sacral agenesis maps to the holoprosencephaly region at 7q36. Author(s): Lynch SA, Bond PM, Copp AJ, Kirwan WO, Nour S, Balling R, Mariman E, Burn J, Strachan T. Source: Nature Genetics. 1995 September; 11(1): 93-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7550324

•

A male infant with holoprosencephaly, associated with ring chromosome 21. Author(s): Aronson DC, Jansweijer MC, Hoovers JM, Barth PG. Source: Clinical Genetics. 1987 January; 31(1): 48-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3568433

•

A new clue to the prenatal diagnosis of lobar holoprosencephaly: the abnormal pathway of the anterior cerebral artery crawling under the skull. Author(s): Bernard JP, Drummond CL, Zaarour P, Molho M, Ville Y. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2002 June; 19(6): 605-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12099261

•

A new mutation in the six-domain of SIX3 gene causes holoprosencephaly. Author(s): Pasquier L, Dubourg C, Blayau M, Lazaro L, Le Marec B, David V, Odent S. Source: European Journal of Human Genetics : Ejhg. 2000 October; 8(10): 797-800. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11039582

•

A novel mutation of the human 7-dehydrocholesterol reductase gene reduces enzyme activity in patients with holoprosencephaly. Author(s): Shim YH, Bae SH, Kim JH, Kim KR, Kim CJ, Paik YK. Source: Biochemical and Biophysical Research Communications. 2004 February 27; 315(1): 219-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15013448

•

A unilateral cleft lip patient with holoprosencephaly. Author(s): Yonehara Y, Takato T, Komori T. Source: Annals of Plastic Surgery. 1997 August; 39(2): 210-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9262780

•

A unique case of holoprosencephaly. Author(s): Potters AE, Schierbeek JM, Jansen W. Source: Prenatal Diagnosis. 1996 October; 16(10): 950-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8938068

24

Holoprosencephaly

•

Abnormal chromosome 18 in prenatal diagnosis with holoprosencephaly. Author(s): de Pater JM, Scheres JM, Brons J. Source: Prenatal Diagnosis. 1997 September; 17(9): 887-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9316141

•

Absence of the superior labial frenulum in holoprosencephaly: a new diagnostic sign. Author(s): Martin RA, Jones KL. Source: The Journal of Pediatrics. 1998 July; 133(1): 151-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9672532

•

Acalvaria, holoprosencephaly, and facial dysmorphism syndrome. Author(s): Sperber GH, Honore LH, Johnson ES. Source: J Craniofac Genet Dev Biol Suppl. 1986; 2: 319-29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3491120

•

Agnathia, holoprosencephaly, and situs inversus. Author(s): Robinson HB Jr, Lenke R. Source: American Journal of Medical Genetics. 1989 October; 34(2): 266-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2817009

•

Agnathia, holoprosencephaly, and situs inversus: report of a case. Author(s): Leech RW, Bowlby LS, Brumback RA, Schaefer GB Jr. Source: American Journal of Medical Genetics. 1988 March; 29(3): 483-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3287921

•

Agnathia-holoprosencephaly: a developmental field complex involving face and brain. Report of 3 cases. Author(s): Bixler D, Ward R, Gale DD. Source: J Craniofac Genet Dev Biol Suppl. 1985; 1: 241-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3932506

•

Agnathia-holoprosencephaly: a new recessive syndrome? Author(s): Porteous ME, Wright C, Smith D, Burn J. Source: Clinical Dysmorphology. 1993 April; 2(2): 161-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8281280

•

Agnathia-holoprosencephaly-situs inversus. Author(s): Ozden S, Ficicioglu C, Kara M, Oral O, Bilgic R. Source: American Journal of Medical Genetics. 2000 March 20; 91(3): 235-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10756350

Studies

25

•

Aicardi syndrome with holoprosencephaly and cleft lip and palate. Author(s): Sato N, Matsuishi T, Utsunomiya H, Yamashita Y, Horikoshi T, Okudera T, Hashimoto T. Source: Pediatric Neurology. 1987 March-April; 3(2): 114-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3508052

•

Airway obstruction due to a rudimentary premaxilla in holoprosencephaly. Author(s): Mehendale FV, Sommerlad BC. Source: The Cleft Palate-Craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association. 2001 May; 38(3): 271-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11386438

•

Alobar holoprosencephaly at 9 weeks gestational age visualized by two- and threedimensional ultrasound. Author(s): Blaas HG, Eik-Nes SH, Vainio T, Isaksen CV. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2000 January; 15(1): 62-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10776015

•

Alobar holoprosencephaly with diabetes insipidus and neuronal migration disorder. Author(s): Takahashi S, Miyamoto A, Oki J, Saino T, Inyaku F. Source: Pediatric Neurology. 1995 September; 13(2): 175-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8534287

•

Alobar holoprosencephaly, diabetes insipidus and coloboma without craniofacial abnormalities: a case report. Author(s): Van Gool S, de Zegher F, de Vries LS, Vanderschueren-Lodeweyckx M, Devlieger H, Casaer P, Eggermont E. Source: European Journal of Pediatrics. 1990 June; 149(9): 621-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2373111

•

Alobar holoprosencephaly. Author(s): Selden NS. Source: Pediatric Neurosurgery. 2000 August; 33(2): 112. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11070439

•

Alobar holoprosencephaly: report of two cases with unusual findings. Author(s): Chang LH. Source: Chang Gung Med J. 2003 September; 26(9): 700-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14651170

26

Holoprosencephaly

•

Analysis of the cerebral cortex in holoprosencephaly with attention to the sylvian fissures. Author(s): Barkovich AJ, Simon EM, Clegg NJ, Kinsman SL, Hahn JS. Source: Ajnr. American Journal of Neuroradiology. 2002 January; 23(1): 143-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11827887

•

Anatomy of the circle of Willis in three cases of human fetal synophthalmic holoprosencephaly. Author(s): Arnold WH, Sperber GH, Machin GA. Source: Anat Anz. 1996 December; 178(6): 553-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9010572

•

Anesthetic considerations in holoprosencephaly. Author(s): Katende RS, Herlich A. Source: Anesthesia and Analgesia. 1987 September; 66(9): 908-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3619099

•

Another holoprosencephaly locus at 7q21.2? Author(s): Fryns JP. Source: Journal of Medical Genetics. 1998 July; 35(7): 614-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9678712

•

Anterior callosal agenesis in mild, lobar holoprosencephaly. Author(s): Sener RN. Source: Pediatric Radiology. 1995; 25(5): 385-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7567274

•

Apolipoprotein B and apolipoprotein E genotypes and sporadic holoprosencephaly. Author(s): Croen LA, Shaw GM, Barber RC, Baker MM, Finnell RH, Lammer EJ. Source: American Journal of Medical Genetics. 2002 February 15; 108(1): 75-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11857554

•

Apparent atypical callosal dysgenesis: analysis of MR findings in six cases and their relationship to holoprosencephaly. Author(s): Barkovich AJ. Source: Ajnr. American Journal of Neuroradiology. 1990 March-April; 11(2): 333-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1690501

Studies

27

•

Assessment of the deep gray nuclei in holoprosencephaly. Author(s): Simon EM, Hevner R, Pinter JD, Clegg NJ, Miller VS, Kinsman SL, Hahn JS, Barkovich AJ. Source: Ajnr. American Journal of Neuroradiology. 2000 November-December; 21(10): 1955-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11110554

•

Association of holoprosencephaly and Down syndrome. Author(s): Martinez-Frias ML. Source: American Journal of Medical Genetics. 1989 March; 32(3): 435. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2524971

•

Association of holoprosencephaly, ectrodactyly, cleft lip/cleft palate and hypertelorism: a possible third case. Author(s): Imaizumi K, Ishii T, Masuno M, Kuroki Y. Source: Clinical Dysmorphology. 1998 July; 7(3): 213-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9689997

•

Atelencephalic microcephaly: craniofacial anatomy and morphologic comparisons with holoprosencephaly and anencephaly. Author(s): Siebert JR, Kokich VG, Warkany J, Lemire RJ. Source: Teratology. 1987 December; 36(3): 279-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3424215

•

Autosomal recessive alobar holoprosencephaly with cyclops in three female sibs: prenatal ultrasonographic diagnosis at 18th week. Author(s): Balci S, Onol B, Ercal MD, Gunay M, Besim A, Eryilmaz M. Source: Clinical Dysmorphology. 1993 April; 2(2): 165-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8281281

•

Autosomal recessive alobar holoprosencephaly with essentially normal faces. Author(s): Barr M Jr, Cohen MM Jr. Source: American Journal of Medical Genetics. 2002 September 15; 112(1): 28-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12239716

•

Aventriculi associated with holoprosencephaly. Author(s): Sener RN. Source: Computerized Medical Imaging and Graphics : the Official Journal of the Computerized Medical Imaging Society. 1998 July-August; 22(4): 345-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9840665

28

Holoprosencephaly

•

Bilateral brachial amelia with facial clefts and holoprosencephaly. Author(s): Thomas M, Donnai D. Source: Clinical Dysmorphology. 1994 July; 3(3): 266-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7981864

•

Brains and faces in holoprosencephaly: pre- and postnatal description of 30 cases. Author(s): Blaas HG, Eriksson AG, Salvesen KA, Isaksen CV, Christensen B, Mollerlokken G, Eik-Nes SH. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2002 January; 19(1): 24-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11851965

•

Cebocephaly, alobar holoprosencephaly, spina bifida, and sirenomelia in a stillbirth. Author(s): Chen CP, Shih SL, Liu FF, Jan SW. Source: Journal of Medical Genetics. 1997 March; 34(3): 252-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9132501

•

Cerebral retroflexion in holoprosencephaly developed following ventriculoperitoneal shunting: a case report. Author(s): Nagane M, Tsuchida T, Takemura N, Hayakawa I. Source: Surgical Neurology. 1993 October; 40(4): 314-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8211642

•

Chance vs. causality in the association of Down syndrome and holoprosencephaly. Author(s): Epstein CJ, Seto S, Golabi M. Source: American Journal of Medical Genetics. 1988 August; 30(4): 939-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2973235

•

Chromosomal localization in mouse and human of the vasoactive intestinal peptide receptor type 2 gene: a possible contributor to the holoprosencephaly 3 phenotype. Author(s): Mackay M, Fantes J, Scherer S, Boyle S, West K, Tsui LC, Belloni E, Lutz E, Van Heyningen V, Harmar AJ. Source: Genomics. 1996 November 1; 37(3): 345-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8938447

•

Chromosome 7 abnormalities in parents of children with holoprosencephaly and hydronephrosis. Author(s): Lurie IW, Ilyina HG, Podleschuk LV, Gorelik LB, Zaletajev DV. Source: American Journal of Medical Genetics. 1990 February; 35(2): 286-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2309771

Studies

29

•

Chronic hypernatremia associated with holoprosencephaly. Author(s): Ohtake M, Suzuki H, Igarashi Y, Kobayashi Y, Saito T. Source: The Tohoku Journal of Experimental Medicine. 1979 August; 128(4): 333-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=483301

•

Clinical and neuropathological investigations of four cases of holoprosencephaly with arhinencephaly. Author(s): Habedank M, Thomas E. Source: Neuropadiatrie. 1970 December; 2(2): 144-63. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5001028

•

Clinical, cytogenetic, and molecular approaches to the genetic heterogeneity of holoprosencephaly. Author(s): Munke M. Source: American Journal of Medical Genetics. 1989 October; 34(2): 237-45. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2683787

•

Coexistent holoprosencephaly and Chiari II malformation. Author(s): Rollins N, Joglar J, Perlman J. Source: Ajnr. American Journal of Neuroradiology. 1999 October; 20(9): 1678-81. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10543640

•

Complete median cleft of the upper lip and alveolus with holoprosencephaly. Author(s): Mizuno A, Kawabata T, Kamiya H, Nakamura T, Motegi K, Hongo T, Ogawa H, Toya K, Igarashi Y, Nakamura S. Source: International Journal of Oral and Maxillofacial Surgery. 1986 August; 15(4): 47882. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3091731

•

Computed tomography evaluation of holoprosencephaly in infants and children. Author(s): Byrd SE, Harwood-Nash DC, Fitz CR, Rogovitz DM. Source: Journal of Computer Assisted Tomography. 1977 October; 1(4): 456-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=615225

•

Congenital nasal pyriform aperture stenosis as a presenting feature of holoprosencephaly. Author(s): Hui Y, Friedberg J, Crysdale WS. Source: International Journal of Pediatric Otorhinolaryngology. 1995 March; 31(2-3): 26374. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7782184

30

Holoprosencephaly

•

Congenital nasal pyriform aperture stenosis in the monozygotic twin of a child with holoprosencephaly. Author(s): Krol BJ, Hulka GF, Drake A. Source: Otolaryngology and Head and Neck Surgery. 1998 May; 118(5): 679-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9591870

•

Criteria for the prenatal diagnosis of holoprosencephaly. Author(s): Pilu G, Romero R, Rizzo N, Jeanty P, Bovicelli L, Hobbins JC. Source: American Journal of Perinatology. 1987 January; 4(1): 41-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3539134

•

CT findings in an alobar holoprosencephaly associated with Dandy-Walker's cyst. Author(s): Hayashi T, Kuramoto S, Takagi S, Kojyo N, Nakayama K. Source: Kurume Med J. 1980; 27(2): 139-42. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7431815

•

Cyclopia-astomia-agnathia-holoprosencephaly association: a case report. Author(s): Sezgin I, Sungu S, Bekar E, Cetin M, Ceran H. Source: Clinical Dysmorphology. 2002 July; 11(3): 225-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12072809

•

Cyclopia-otocephaly association: a new case of the most severe variant of agnathiaholoprosencephaly complex. Author(s): Carles D, Serville F, Mainguene M, Dubecq JP. Source: Journal of Craniofacial Genetics and Developmental Biology. 1987; 7(2): 107-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3114309

•

Cytogenetic rearrangements involving the loss of the Sonic Hedgehog gene at 7q36 cause holoprosencephaly. Author(s): Roessler E, Ward DE, Gaudenz K, Belloni E, Scherer SW, Donnai D, SiegelBartelt J, Tsui LC, Muenke M. Source: Human Genetics. 1997 August; 100(2): 172-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9254845

•

Cytogenetic variants in holoprosencephaly. Report of a case and review of the literature. Author(s): Ming PM, Goodner DM, Park TS. Source: Am J Dis Child. 1976 August; 130(8): 864-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=941887

Studies

31

•

De novo 7q36 deletion: breakpoint analysis and types of holoprosencephaly. Author(s): Frints SG, Schoenmakers EF, Smeets E, Petit P, Fryns JP. Source: American Journal of Medical Genetics. 1998 January 13; 75(2): 153-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9450876

•

De novo interstitial proximal deletion of 14q and prenatal diagnosis of holoprosencephaly. Author(s): Bruyere H, Favre B, Douvier S, Nivelon-Chevalier A, Mugneret F. Source: Prenatal Diagnosis. 1996 November; 16(11): 1059-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8953644

•

Dendritic overgrowth and alterations in laminar phenotypes of neocortical neurons in the newborn with semilobar holoprosencephaly. Author(s): Judas M, Rasin MR, Kruslin B, Kostovic K, Jukic D, Petanjek Z, Kostovic I. Source: Brain & Development. 2003 January; 25(1): 32-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12536031

•

Descriptive epidemiology of holoprosencephaly and arhinencephaly in metropolitan Atlanta, 1968-1992. Author(s): Rasmussen SA, Moore CA, Khoury MJ, Cordero JF. Source: American Journal of Medical Genetics. 1996 December 18; 66(3): 320-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8985495

•

Diagnosis and management of fetal holoprosencephaly. Author(s): Chervenak FA, Isaacson G, Hobbins JC, Chitkara U, Tortora M, Berkowitz RL. Source: Obstetrics and Gynecology. 1985 September; 66(3): 322-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3895078

•

Different proximal and distal rearrangements of chromosome 7q associated with holoprosencephaly. Author(s): Benzacken B, Siffroi JP, Le Bourhis C, Krabchi K, Joye N, Maschino F, Viguie F, Soulie J, Gonzales M, Migne G, Bucourt M, Encha-Razavi F, Carbillon L, Taillemite JL. Source: Journal of Medical Genetics. 1997 November; 34(11): 899-903. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9391882

•

Disorders of midline structures: holoprosencephaly, absence of corpus callosum, and Chiari malformations. Author(s): Byrd SE, Osborn RE, Radkowski MA, McArdle CB, Prenger EC, Naidich TP. Source: Semin Ultrasound Ct Mr. 1988 June; 9(3): 201-15. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3078668

32

Holoprosencephaly

•

Distribution of leptomeningeal glioneuronal heterotopia in alobar holoprosencephaly. Author(s): Mizuguchi M, Maekawa S, Kamoshita S. Source: Archives of Neurology. 1994 September; 51(9): 951-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8080397

•

Dominant inheritance of holoprosencephaly. Author(s): Cantu JM, Fragoso R, Garcia-Cruz D, Sanchez-Corona J. Source: Birth Defects Orig Artic Ser. 1978; 14(6B): 215-20. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=728563

•

Dorsal cyst malformations. Part I. Clinical study and critical review on the definition of holoprosencephaly. Author(s): Yokota A, Oota T, Matsukado Y. Source: Childs Brain. 1984; 11(5): 320-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6389035

•

Dorsal third ventricular cyst: an entity distinct from holoprosencephaly. Author(s): Young JN, Oakes WJ, Hatten HP Jr. Source: Journal of Neurosurgery. 1992 October; 77(4): 556-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1527614

•

Dysgenesis of the deep venous system as a diagnostic criterion for holoprosencephaly. Author(s): Osaka K, Sato N, Yamasaki S, Fujita K, Matsumoto S. Source: Neuroradiology. 1977 July 29; 13(5): 231-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=896030

•

Dysmorphology report holoprosencephaly-polydactyly syndrome: affected brother and sister with a wide spectrum of anomalies. Author(s): Delozier-Blanchet CD, Engel E. Source: Genet Couns. 1992; 3(1): 57-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1590983

•

Early diagnosis of holoprosencephaly. Author(s): Nelson LH, King M. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 1992 January; 11(1): 57-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1740835

Studies

33

•

Early prenatal diagnosis of cyclopia associated with holoprosencephaly. Author(s): Toth Z, Csecsei K, Szeifert G, Torok O, Papp Z. Source: Journal of Clinical Ultrasound : Jcu. 1986 September; 14(7): 550-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3095383

•

Early prenatal diagnosis of holoprosencephaly: the value of transvaginal ultrasonography. Author(s): Stagiannis KD, Sepulveda W, Bower S. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1995 August; 61(2): 175-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7556842

•

Early transvaginal sonographic diagnosis of alobar holoprosencephaly. Author(s): Bronshtein M, Wiener Z. Source: Prenatal Diagnosis. 1991 July; 11(7): 459-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1754562

•

Ectopic expression of telencephalin in brains with holoprosencephaly. Author(s): Arii N, Mizuguchi M, Mori K, Takashima S. Source: Acta Neuropathologica. 2000 November; 100(5): 506-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11045672

•

EEG recognition of holoprosencephaly and Aicardi syndrome. Author(s): Shah KN, Rajadhyaksha S, Shah VS, Wakde M. Source: Indian J Pediatr. 1992 January-February; 59(1): 103-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1612653

•

Electroencephalography in holoprosencephaly: findings in children without epilepsy. Author(s): Hahn JS, Delgado MR, Clegg NJ, Sparagana SP, Gerace KL, Barkovich AJ, Olson DM. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2003 October; 114(10): 1908-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14499753

•

Embryonic origin of holoprosencephaly: interrelationship of the developing brain and face. Author(s): Sulik KK, Johnston MC. Source: Scan Electron Microsc. 1982; (Pt 1): 309-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7167750

34

Holoprosencephaly

•

Epidemiology of holoprosencephaly and phenotypic characteristics of affected children: New York State, 1984-1989. Author(s): Olsen CL, Hughes JP, Youngblood LG, Sharpe-Stimac M. Source: American Journal of Medical Genetics. 1997 December 12; 73(2): 217-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9409876

•

Epidemiology of holoprosencephaly in Hawaii, 1986-97. Author(s): Forrester MB, Merz RD. Source: Paediatric and Perinatal Epidemiology. 2000 January; 14(1): 61-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10703035

•

Epileptic seizures and structural abnormalities in a patient with holoprosencephaly. Author(s): Takahashi S, Takahashi Y, Kondo N, Orii T. Source: Brain & Development. 2001 July; 23(4): 264-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11377010

•

Expression of the Sonic hedgehog (SHH ) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly. Author(s): Odent S, Atti-Bitach T, Blayau M, Mathieu M, Aug J, Delezo de AL, Gall JY, Le Marec B, Munnich A, David V, Vekemans M. Source: Human Molecular Genetics. 1999 September; 8(9): 1683-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10441331

•

Extramedullary hematopoiesis within a frontoethmoidal encephalocele in a newborn with holoprosencephaly. Author(s): Elgin VE, Connolly ES, Millar WS, Feldstein NA, Dwork AJ. Source: Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 2001 May-June; 4(3): 289-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11370267

•

Extreme variability of expression of a Sonic Hedgehog mutation: attention difficulties and holoprosencephaly. Author(s): Heussler HS, Suri M, Young ID, Muenke M. Source: Archives of Disease in Childhood. 2002 April; 86(4): 293-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11919111

•

Familial agnathia-holoprosencephaly caused by an inherited unbalanced translocation and not autosomal recessive inheritance. Author(s): Krassikoff N, Sekhon GS. Source: American Journal of Medical Genetics. 1989 October; 34(2): 255-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2817007

Studies

35

•

Familial agnathia-holoprosencephaly. Author(s): Pauli RM, Pettersen JC, Arya S, Gilbert EF. Source: American Journal of Medical Genetics. 1983 April; 14(4): 677-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6846401

•

Familial holoprosencephaly associated with a translocation breakpoint at chromosomal position 7q36. Author(s): Hatziioannou AG, Krauss CM, Lewis MB, Halazonetis TD. Source: American Journal of Medical Genetics. 1991 August 1; 40(2): 201-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1897576

•

Familial holoprosencephaly with endocrine dysgenesis. Author(s): Hintz RL, Menking M, Sotos JF. Source: The Journal of Pediatrics. 1968 January; 72(1): 81-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4294576

•

Familial holoprosencephaly with median cleft lip. Author(s): Godeano D, Winter ST, Dar H. Source: J Genet Hum. 1973 September; 21(3): 223-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4805911

•

Familial holoprosencephaly, heart defects, and polydactyly. Author(s): Hennekam RC, van Noort G, de la Fuente AA. Source: American Journal of Medical Genetics. 1991 November 1; 41(2): 258-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1785646

•

Familial holoprosencephaly. Author(s): Dallaire L, Fraser FC, Wiglesworth FW. Source: Birth Defects Orig Artic Ser. 1971 June; 7(7): 136-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5173201

•

Familial holoprosencephaly. Author(s): Khan M, Rozdilsky B, Gerrard JW. Source: Developmental Medicine and Child Neurology. 1970 February; 12(1): 71-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5309311

•

Familial holoprosencephaly. Author(s): Escobar V, Cantu JM, Martin AO. Source: Clinical Genetics. 1979 February; 15(2): 203-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=761422

36

Holoprosencephaly

•

Familial holoprosencephaly: further example of autosomal recessive inheritance. Author(s): Gillessen-Kaesbach G. Source: Birth Defects Orig Artic Ser. 1996; 30(1): 251-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9125332

•

Features within the holoprosencephaly spectrum in sibs with a Robertsonian (14q;22q) translocation chromosome. Author(s): Kamnasaran D, Gerritsen JA, McLeod DR, Cox DW. Source: Clinical Genetics. 2001 September; 60(3): 237-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11595027

•

Fetal holoprosencephaly: associated malformations and chromosomal defects. Author(s): Berry SM, Gosden C, Snijders RJ, Nicolaides KH. Source: Fetal Diagnosis and Therapy. 1990; 5(2): 92-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2130835

•

First trimester diagnosis of cyclopia and holoprosencephaly. Author(s): van Zalen-Sprock R, van Vugt JM, van der Harten HJ, Nieuwint AW, van Geijn HP. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 1995 August; 14(8): 631-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7474065

•

First trimester diagnosis of holoprosencephaly and cyclopia with triploidy by transvaginal three-dimensional ultrasonography. Author(s): Hsu TY, Chang SY, Ou CY, Chen ZH, Tsai WL, Chang MS, Soong YK. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2001 June; 96(2): 235-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11384818

•

First trimester diagnosis of holoprosencephaly with a Dandy-Walker malformation by transvaginal ultrasonography. Author(s): Gembruch U, Baschat AA, Reusche E, Wallner SJ, Greiwe M. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 1995 August; 14(8): 619-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7474062

•

First trimester sonographic diagnosis of holoprosencephaly. Author(s): Tongsong T, Wanapirak C, Chanprapaph P, Siriangkul S. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1999 August; 66(2): 165-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10468341

Studies

37

•

First-trimester ultrasound diagnosis of holoprosencephaly: three case reports. Author(s): Wong HS, Lam YH, Tang MH, Cheung LW, Ng LK, Yan KW. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 1999 May; 13(5): 356-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10380302

•

Forebrain cleavage gene causing holoprosencephaly: deletion mapping to chromosome band 2p21. Author(s): Hecht BK, Hecht F, Munke M. Source: American Journal of Medical Genetics. 1991 July 1; 40(1): 130. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1887845

•

From holoprosencephaly to osteopathology: role of multifunctional endocytic receptors in absorptive epithelia. Author(s): Muller D, Nykjaer A, Willnow TE. Source: Annals of Medicine. 2003; 35(5): 290-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12952015

•

Frontonasal dysplasia as an expression of holoprosencephaly. Author(s): Roubicek M, Spranger J, Wende S. Source: European Journal of Pediatrics. 1981 October; 137(2): 229-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7308235

•

Fundal uterine leiomyoma obscuring first-trimester transabdominal sonographic diagnosis of fetal holoprosencephaly. A case report. Author(s): Sakala EP, Gaio KL. Source: J Reprod Med. 1993 May; 38(5): 400-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8320680

•

Gelastic seizure with tectal tumor, lobar holoprosencephaly, and subependymal nodules: clinical report. Author(s): Akman CI, Schubert R, Duran M, Loh J. Source: Journal of Child Neurology. 2002 February; 17(2): 152-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11952080

•

Generalized chorea in an infant with semilobar holoprosencephaly. Author(s): Louis ED, Lynch T, Cargan AL, Fahn S. Source: Pediatric Neurology. 1995 November; 13(4): 355-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8771177

38

Holoprosencephaly

•

Genetic approaches to understanding brain development: holoprosencephaly as a model. Author(s): Muenke M, Cohen MM Jr. Source: Mental Retardation and Developmental Disabilities Research Reviews. 2000; 6(1): 15-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10899793

•

Genetic counselling in holoprosencephaly. Author(s): Burck U. Source: Helv Paediatr Acta. 1982 June; 37(3): 231-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7118555

•

Genetics of ventral forebrain development and holoprosencephaly. Author(s): Muenke M, Beachy PA. Source: Current Opinion in Genetics & Development. 2000 June; 10(3): 262-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10826992

•

Giant glioependymal cyst resembling holoprosencephaly on prenatal ultrasound: case report and review of the literature. Author(s): Pelkey TJ, Ferguson JE 2nd, Veille JC, Alston SR. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 1997 March; 9(3): 200-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9165685

•

Heterotaxy-neural tube defect and holoprosencephaly occuring independently in two sib fetuses. Author(s): Bonneau D, Marechaud M, Odent S, Piegay I, Godard A, Amati P. Source: American Journal of Medical Genetics. 1999 June 4; 84(4): 373-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10340655

•

Histological findings in a case of alobar holoprosencephaly diagnosed at 10 weeks of pregnancy. Author(s): Wong HS, Tang MH, Yan KW, Cheung LW. Source: Prenatal Diagnosis. 1999 September; 19(9): 859-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10521846

•

Holoprosencephaly (lobar form) associated with bilateral vocal cord palsy. Author(s): Smilari P, Serra A, La Mantia I, Parano E, Pavone P. Source: Journal of Child Neurology. 2001 December; 16(12): 932-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11785509

Studies

39

•

Holoprosencephaly and cyclopia visualized by two- and three-dimensional prenatal ultrasound. Author(s): Lee YY, Lin MT, Lee MS, Lin LY. Source: Chang Gung Med J. 2002 March; 25(3): 207-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12022743

•

Holoprosencephaly and low molecular weight proteinuria: the human homologue of murine megalin deficiency. Author(s): Muller D, Ankermann T, Stephani U, Kirschstein M, Szelestei T, Luft FC, Willnow TE. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 2001 March; 37(3): 624-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11228189

•

Holoprosencephaly and split hand/foot: an additional case with this rare association. Author(s): Abdel-Meguid N, Ashour AM. Source: Clinical Dysmorphology. 2001 October; 10(4): 277-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11666003

•

Holoprosencephaly associated with an apparent isolated 2q37.1-->2q37.3 deletion. Author(s): Lehman NL, Zaleski DH, Sanger WG, Adickes ED. Source: American Journal of Medical Genetics. 2001 May 1; 100(3): 179-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11343300

•

Holoprosencephaly at 10 weeks 2 days (CRL 33 mm). Author(s): Blaas HG. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2000 January; 15(1): 86-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10776022

•

Holoprosencephaly due to mutations in ZIC2, a homologue of Drosophila oddpaired. Author(s): Brown SA, Warburton D, Brown LY, Yu CY, Roeder ER, Stengel-Rutkowski S, Hennekam RC, Muenke M. Source: Nature Genetics. 1998 October; 20(2): 180-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9771712

•

Holoprosencephaly due to mutations in ZIC2: alanine tract expansion mutations may be caused by parental somatic recombination. Author(s): Brown LY, Odent S, David V, Blayau M, Dubourg C, Apacik C, Delgado MA, Hall BD, Reynolds JF, Sommer A, Wieczorek D, Brown SA, Muenke M. Source: Human Molecular Genetics. 2001 April 1; 10(8): 791-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11285244

40

Holoprosencephaly

•

Holoprosencephaly in a Klinefelter fetus. Author(s): Armbruster-Moraes E, Schultz R, Brizot MD, Miyadahira S, Zugaib M. Source: American Journal of Medical Genetics. 1999 August 27; 85(5): 511-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10405452

•

Holoprosencephaly in children: diffusion tensor MR imaging of white matter tracts of the brainstem--initial experience. Author(s): Albayram S, Melhem ER, Mori S, Zinreich SJ, Barkovich AJ, Kinsman SL. Source: Radiology. 2002 June; 223(3): 645-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12034930

•

Holoprosencephaly in deletions of proximal chromosome 14q. Author(s): Devriendt K, Fryns JP, Chen CP. Source: Journal of Medical Genetics. 1998 July; 35(7): 612. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9678710

•

Holoprosencephaly survival and performance. Author(s): Barr M Jr, Cohen MM Jr. Source: American Journal of Medical Genetics. 1999 June 25; 89(2): 116-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10559767

•

Holoprosencephaly with cyclopia--report of a pathological study. Author(s): Arathi N, Mahadevan A, Santosh V, Yasha TC, Shankar SK. Source: Neurology India. 2003 June; 51(2): 279-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571030

•

Holoprosencephaly, bilateral cleft lip and palate and ectrodactyly: another case and follow up. Author(s): Konig R, Beeg T, Tariverdian G, Scheffer H, Bitter K. Source: Clinical Dysmorphology. 2003 October; 12(4): 221-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14564207

•

Holoprosencephaly, hypertelorism, and ectrodactyly in a boy with an apparently balanced de novo t(2;4) (q14.2;q35). Author(s): Corona-Rivera A, Corona-Rivera JR, Bobadilla-Morales L, Garcia-Cobian TA, Corona-Rivera E. Source: American Journal of Medical Genetics. 2000 February 28; 90(5): 423-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10706364

Studies

41

•

Holoprosencephaly, sacral anomalies, and situs ambiguus in an infant with partial monosomy 7q/trisomy 2p and SHH and HLXB9 haploinsufficiency. Author(s): Nowaczyk MJ, Huggins MJ, Tomkins DJ, Rossi E, Ramsay JA, Woulfe J, Scherer SW, Belloni E. Source: Clinical Genetics. 2000 May; 57(5): 388-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10852374

•

Holoprosencephaly. Author(s): Thomas NA, Cherian A, Sridhar S. Source: Journal of Postgraduate Medicine. 2003 April-June; 49(2): 173-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12867699

•

Holoprosencephaly. Author(s): Peebles DM. Source: Prenatal Diagnosis. 1998 May; 18(5): 477-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9621381

•

Holoprosencephaly: a defect in brain patterning. Author(s): Golden JA. Source: Journal of Neuropathology and Experimental Neurology. 1998 November; 57(11): 991-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9825935

•

Holoprosencephaly: a paradigm for the complex genetics of brain development. Author(s): Roessler E, Muenke M. Source: Journal of Inherited Metabolic Disease. 1998 August; 21(5): 481-97. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9728329

•

Holoprosencephaly: from Homer to Hedgehog. Author(s): Ming JE, Muenke M. Source: Clinical Genetics. 1998 March; 53(3): 155-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9630065

•

Holoprosencephaly: genetic, neuroradiological, and clinical advances. Author(s): Hahn JS, Pinter JD. Source: Semin Pediatr Neurol. 2002 December; 9(4): 309-19. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12523555

•

Holoprosencephaly: molecular study of a California population. Author(s): Nanni L, Croen LA, Lammer EJ, Muenke M. Source: American Journal of Medical Genetics. 2000 February 14; 90(4): 315-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10710230

42

Holoprosencephaly

•

Holoprosencephaly: new concepts. Author(s): Simon EM, Barkovich AJ. Source: Magn Reson Imaging Clin N Am. 2001 February; 9(1): 149-64, Viii-Ix. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11278187

•

Holoprosencephaly: recent advances and new insights. Author(s): Kinsman SL, Plawner LL, Hahn JS. Source: Current Opinion in Neurology. 2000 April; 13(2): 127-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10987568

•

Holoprosencephaly: the face predicts the brain; the image predicts its function. Author(s): Patterson MC. Source: Neurology. 2002 December 24; 59(12): 1833-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12499471

•

Holoprosencephaly: the Maastricht experience. Author(s): Moog U, De Die-Smulders CE, Schrander-Stumpel CT, Engelen JJ, Hamers AJ, Frints S, Fryns JP. Source: Genet Couns. 2001; 12(3): 287-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11693794

•

How a Hedgehog might see holoprosencephaly. Author(s): Roessler E, Muenke M. Source: Human Molecular Genetics. 2003 April 1; 12 Spec No 1: R15-25. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12668593

•

Hypodipsia-hypernatremia syndrome associated with holoprosencephaly in a child: a case report. Author(s): Karabay-Bayazit A, Herguner O, Altunbasak S, Noyan A, Yukel B, Anarat A. Source: Turk J Pediatr. 2002 July-September; 44(3): 263-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12405444

•

Identification of novel mutations in SHH and ZIC2 in a South American (ECLAMC) population with holoprosencephaly. Author(s): Orioli IM, Castilla EE, Ming JE, Nazer J, Burle de Aguiar MJ, Llerena JC, Muenke M. Source: Human Genetics. 2001 July; 109(1): 1-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11479728

Studies

43

•

Identification of Sonic hedgehog as a candidate gene responsible for holoprosencephaly. Author(s): Belloni E, Muenke M, Roessler E, Traverso G, Siegel-Bartelt J, Frumkin A, Mitchell HF, Donis-Keller H, Helms C, Hing AV, Heng HH, Koop B, Martindale D, Rommens JM, Tsui LC, Scherer SW. Source: Nature Genetics. 1996 November; 14(3): 353-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8896571

•

Identification of unexpected parental Robertsonian (13q;14q) translocations following prenatal sonographic detection of holoprosencephaly. Author(s): Chen CP. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2002 September; 20(3): 304-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12230460

•

In utero sonographic diagnosis of semilobar holoprosencephaly. Author(s): Filice C, Maserati R, Brunetti E, Minoli L, Suter F. Source: Biol Res Pregnancy Perinatol. 1985; 6(3): 112-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3914909

•

Inverted duplication of the distal short arm of chromosome 3 associated with lobar holoprosencephaly and lumbosacral meningomyelocele. Author(s): Kennedy D, Silver MM, Winsor EJ, Toi A, Provias J, Macha M, Precht K, Ledbetter DH, Chitayat D. Source: American Journal of Medical Genetics. 2000 March 20; 91(3): 167-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10756335

•

Investigation of the epidemiology and prenatal diagnosis of holoprosencephaly in the North of England. Author(s): Bullen PJ, Rankin JM, Robson SC. Source: American Journal of Obstetrics and Gynecology. 2001 May; 184(6): 1256-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11349198

•

Isochromosome 18q in a girl with holoprosencephaly, DiGeorge anomaly, and streak ovaries. Author(s): van Essen AJ, Schoots CJ, van Lingen RA, Mourits MJ, Tuerlings JH, Leegte B. Source: American Journal of Medical Genetics. 1993 August 1; 47(1): 85-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8368259

44

Holoprosencephaly

•

Isolation of a 370 kb YAC fragment spanning a translocation breakpoint at 3p14.1 associated with holoprosencephaly. Author(s): Petek E, Kroisel PM, Wagner K. Source: Clinical Genetics. 1998 November; 54(5): 406-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9842993

•

Karyotype 47,XXY,18p--in a newborn child with holoprosencephaly. Author(s): Schnabel R, Hansen S. Source: Clinical Genetics. 1983 March; 23(3): 186-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6851214

•

Lambotte syndrome: microcephaly, holoprosencephaly, intrauterine growth retardation, facial anomalies, and early lethality--a new sublethal multiple congenital anomaly/mental retardation syndrome in four sibs. Author(s): Verloes A, Dodinval P, Beco L, Bonnivert J, Lambotte C. Source: American Journal of Medical Genetics. 1990 September; 37(1): 119-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2240028

•

Letter: Holoprosencephaly revisited. Author(s): Cohen MM Jr. Source: Am J Dis Child. 1974 April; 127(4): 597. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4856605

•

Letter: Holoprosencephaly. Author(s): Lowry RB. Source: Am J Dis Child. 1974 December; 128(6): 887. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4440659

•

Linkage of a human brain malformation, familial holoprosencephaly, to chromosome 7 and evidence for genetic heterogeneity. Author(s): Muenke M, Gurrieri F, Bay C, Yi DH, Collins AL, Johnson VP, Hennekam RC, Schaefer GB, Weik L, Lubinsky MS, et al. Source: Proceedings of the National Academy of Sciences of the United States of America. 1994 August 16; 91(17): 8102-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8058764

•

Lobar holoprosencephaly and Xq22 deletion. Author(s): Petit P, Moerman P, Fryns JP. Source: Genet Couns. 1991; 2(2): 119-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1781956

Studies

45

•

Lobar holoprosencephaly in an infant born to a mother with classic phenylketonuria. Author(s): Keller K, McCune H, Williams C, Muenke M. Source: American Journal of Medical Genetics. 2000 November 13; 95(2): 187-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11078575

•

Lobar holoprosencephaly presenting as spastic diplegia. Author(s): Shanks DE, Wilson WG. Source: Developmental Medicine and Child Neurology. 1988 June; 30(3): 383-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3402680

•

Lobar holoprosencephaly with hydrocephalus: antenatal demonstration and differential diagnosis. Author(s): Hoffman-Tretin JC, Horoupian DS, Koenigsberg M, Schnur MJ, Llena JF. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 1986 December; 5(12): 691-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3543388

•

Lobar holoprosencephaly with vocal cord palsy. Author(s): Hahn JS. Source: Journal of Child Neurology. 2003 February; 18(2): 152; Author Reply 152. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12693788

•

Lobar holoprosencephaly. Author(s): Flores-Sarnat L, Sarnat HB. Source: Journal of Child Neurology. 2002 July; 17(7): 543; Author Reply 543-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12269737

•

Loss-of-function mutations in the human GLI2 gene are associated with pituitary anomalies and holoprosencephaly-like features. Author(s): Roessler E, Du YZ, Mullor JL, Casas E, Allen WP, Gillessen-Kaesbach G, Roeder ER, Ming JE, Ruiz i Altaba A, Muenke M. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 November 11; 100(23): 13424-9. Epub 2003 October 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14581620

•

Median cleft face syndrome in association with hydrocephalus, agenesis of the corpus callosum, holoprosencephaly and choanal atresia. Author(s): Bomelburg T, Lenz W, Eusterbrock T. Source: European Journal of Pediatrics. 1987 May; 146(3): 301-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3595651

46

Holoprosencephaly

•

Median cleft lip with holoprosencephaly. Author(s): Tan KL. Source: Aust Paediatr J. 1973 February; 9(1): 31-4. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4708026

•

Median cleft lip without holoprosencephaly. Case report. Author(s): van der Wal KG, Wiebe Mulder J. Source: International Journal of Oral and Maxillofacial Surgery. 1993 February; 22(1): 3941. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8459121

•

Mediobasal and mantle defect of the prosencephalon: lobar holoprosencephaly, schizencephaly and diabetes insipidus. Author(s): Sztriha L, Varady E, Hertecant J, Nork M. Source: Neuropediatrics. 1998 October; 29(5): 272-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9810564

•

Mediobasal prosencephalic defects, including holoprosencephaly and cyclopia, in relation to the development of the human forebrain. Author(s): Muller F, O'Rahilly R. Source: Am J Anat. 1989 August; 185(4): 391-414. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2506752

•

Microcephaly in familial holoprosencephaly. Author(s): Ardinger HH, Bartley JA. Source: Journal of Craniofacial Genetics and Developmental Biology. 1988; 8(1): 53-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3209679

•

Microcephaly, holoprosencephaly, hypokinesia--second report of a new syndrome. Author(s): Hockey A, Crowhurst J, Cullity G. Source: Prenatal Diagnosis. 1988 November; 8(9): 683-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3211858

•

Middle interhemispheric fusion: an unusual variant of holoprosencephaly. Author(s): Barkovich AJ, Quint DJ. Source: Ajnr. American Journal of Neuroradiology. 1993 March-April; 14(2): 431-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8456724

Studies

47

•

Middle interhemispheric variant of holoprosencephaly associated with diffuse polymicrogyria. Author(s): Takanashi J, Barkovich AJ, Clegg NJ, Delgado MR. Source: Ajnr. American Journal of Neuroradiology. 2003 March; 24(3): 394-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12637288

•

Middle interhemispheric variant of holoprosencephaly: a distinct cliniconeuroradiologic subtype. Author(s): Lewis AJ, Simon EM, Barkovich AJ, Clegg NJ, Delgado MR, Levey E, Hahn JS. Source: Neurology. 2002 December 24; 59(12): 1860-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12499474

•

Midline interhemispheric fusion associated with atypical callosal dysgenesis: a mild type of holoprosencephaly. Author(s): Sener RN, Jones AO, Roebuck DJ, de Silva M. Source: Australasian Radiology. 1996 August; 40(3): 357-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8826753

•

Midline skeletodental morphology in holoprosencephaly. Author(s): Kjaer I, Keeling JW, Fischer Hansen B, Becktor KB. Source: The Cleft Palate-Craniofacial Journal : Official Publication of the American Cleft Palate-Craniofacial Association. 2002 May; 39(3): 357-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12019014

•

Molecular characterization of breakpoints in patients with holoprosencephaly and definition of the HPE2 critical region 2p21. Author(s): Schell U, Wienberg J, Kohler A, Bray-Ward P, Ward DE, Wilson WG, Allen WP, Lebel RR, Sawyer JR, Campbell PL, Aughton DJ, Punnett HH, Lammer EJ, Kao FT, Ward DC, Muenke M. Source: Human Molecular Genetics. 1996 February; 5(2): 223-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8824878

•

Molecular cytogenetic analysis of patients with holoprosencephaly and structural rearrangements of 7q. Author(s): Vance GH, Nickerson C, Sarnat L, Zhang A, Henegariu O, MorichonDelvallez N, Butler MG, Palmer CG. Source: American Journal of Medical Genetics. 1998 February 26; 76(1): 51-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9508065

48

Holoprosencephaly

•

Molecular diagnosis of a novel heterozygous 268C-->T (R90C) mutation in TGIF gene in a fetus with holoprosencephaly and premaxillary agenesis. Author(s): Chen CP, Chern SR, Du SH, Wang W. Source: Prenatal Diagnosis. 2002 January; 22(1): 5-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11810641

•

Molecular genetics of holoprosencephaly. Author(s): Nanni L, Schelper RL, Muenke MT. Source: Frontiers in Bioscience : a Journal and Virtual Library. 2000 March 1; 5: D334-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10704430

•

Molecular mechanisms of holoprosencephaly. Author(s): Wallis DE, Muenke M. Source: Molecular Genetics and Metabolism. 1999 October; 68(2): 126-38. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10527664

•

Molecular screening of the TGIF gene in holoprosencephaly: identification of two novel mutations. Author(s): Aguilella C, Dubourg C, Attia-Sobol J, Vigneron J, Blayau M, Pasquier L, Lazaro L, Odent S, David V. Source: Human Genetics. 2003 February; 112(2): 131-4. Epub 2002 November 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12522553

•

Monozygosity and holoprosencephaly: cleavage disorders of the "midline field". Author(s): Suslak L, Mimms GM, Desposito F. Source: American Journal of Medical Genetics. 1987 September; 28(1): 99-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3674122

•

Monozygotic twin aborted fetuses discordant for holoprosencephaly/synotia. Author(s): Machin GA, Sperber GH, Wootliffe J. Source: Teratology. 1985 April; 31(2): 203-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3992489

•

Mosaic trisomy 9 and lobar holoprosencephaly. Author(s): Gerard-Blanluet M, Danan C, Sinico M, Lelong F, Borghi E, Dassieu G, Janaud JC, Odent S, Encha-Razavi F. Source: American Journal of Medical Genetics. 2002 August 15; 111(3): 295-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12210326

Studies

49

•

Mouse models of holoprosencephaly. Author(s): Hayhurst M, McConnell SK. Source: Current Opinion in Neurology. 2003 April; 16(2): 135-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644739

•

MRI shows abnormal white matter maturation in classical holoprosencephaly. Author(s): Barkovich AJ, Simon EM, Glenn OA, Clegg NJ, Kinsman SL, Delgado M, Hahn JS. Source: Neurology. 2002 December 24; 59(12): 1968-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12499493

•

Multiple hits during early embryonic development: digenic diseases and holoprosencephaly. Author(s): Ming JE, Muenke M. Source: American Journal of Human Genetics. 2002 November; 71(5): 1017-32. Epub 2002 October 22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12395298

•

Mutations in holoprosencephaly. Author(s): Wallis D, Muenke M. Source: Human Mutation. 2000; 16(2): 99-108. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10923031

•

Mutations in PATCHED-1, the receptor for SONIC HEDGEHOG, are associated with holoprosencephaly. Author(s): Ming JE, Kaupas ME, Roessler E, Brunner HG, Golabi M, Tekin M, Stratton RF, Sujansky E, Bale SJ, Muenke M. Source: Human Genetics. 2002 April; 110(4): 297-301. Epub 2002 March 02. Erratum In: Hum Genet 2002 October; 111(4-5): 464. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11941477

•

Mutations in TGIF cause holoprosencephaly and link NODAL signalling to human neural axis determination. Author(s): Gripp KW, Wotton D, Edwards MC, Roessler E, Ades L, Meinecke P, Richieri-Costa A, Zackai EH, Massague J, Muenke M, Elledge SJ. Source: Nature Genetics. 2000 June; 25(2): 205-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10835638

•

Mutations in the C-terminal domain of Sonic Hedgehog cause holoprosencephaly. Author(s): Roessler E, Belloni E, Gaudenz K, Vargas F, Scherer SW, Tsui LC, Muenke M. Source: Human Molecular Genetics. 1997 October; 6(11): 1847-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9302262

50

Holoprosencephaly

•

Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly. Author(s): Wallis DE, Roessler E, Hehr U, Nanni L, Wiltshire T, Richieri-Costa A, Gillessen-Kaesbach G, Zackai EH, Rommens J, Muenke M. Source: Nature Genetics. 1999 June; 22(2): 196-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10369266

•

Mutations in the human Sonic Hedgehog gene cause holoprosencephaly. Author(s): Roessler E, Belloni E, Gaudenz K, Jay P, Berta P, Scherer SW, Tsui LC, Muenke M. Source: Nature Genetics. 1996 November; 14(3): 357-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8896572

•

Nasal pyriform aperture stenosis and the holoprosencephaly spectrum. Author(s): Tavin E, Stecker E, Marion R. Source: International Journal of Pediatric Otorhinolaryngology. 1994 January; 28(2-3): 199-204. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8157419

•

Neuroanatomy of holoprosencephaly as predictor of function: beyond the face predicting the brain. Author(s): Plawner LL, Delgado MR, Miller VS, Levey EB, Kinsman SL, Barkovich AJ, Simon EM, Clegg NJ, Sweet VT, Stashinko EE, Hahn JS. Source: Neurology. 2002 October 8; 59(7): 1058-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12370462

•

Neuropathologic research strategies in holoprosencephaly. Author(s): Sarnat HB, Flores-Sarnat L. Source: Journal of Child Neurology. 2001 December; 16(12): 918-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11785508

•

Neuropathological evaluation of the diencephalon, basal ganglia and upper brainstem in alobar holoprosencephaly. Author(s): Hayashi M, Araki S, Kumada S, Itoh M, Morimatsu Y, Matsuyama H. Source: Acta Neuropathologica. 2004 March; 107(3): 190-6. Epub 2003 December 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14685895

•

Occipital encephalocele with holoprosencephaly and aqueduct stenosis. Author(s): Hutchison JW, Stovring J, Turner PT. Source: Surgical Neurology. 1979 October; 12(4): 331-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=524253

Studies

51

•

Occurrence of holoprosencephaly in chromosome 13 disorders cannot be explained by duplication/deficiency of a single locus. Author(s): Wilson GN, Dasouki M, Barr M Jr. Source: Am J Med Genet Suppl. 1986; 2: 65-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3146301

•

Ocular coloboma associated with a solitary maxillary central incisor and growth failure: manifestations of holoprosencephaly. Author(s): Liberfarb RM, Abdo OP, Pruett RC. Source: Ann Ophthalmol. 1987 June; 19(6): 226-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3113318

•

Olfactory dysgenesis or hypoplasia: a variant in the arhinencephaly spectrum? Author(s): Louis DN, Arriagada PV, Hyman BT, Hedley-Whyte ET. Source: Neurology. 1992 January; 42(1): 179-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1734299

•

On the association profound nerve deafness, semilobar holoprosencephaly, and minor midline developmental anomalies. Author(s): Vantrappen G, Feenstra L, Fryns JP. Source: Genet Couns. 1999; 10(4): 399-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10631930

•

Otocephaly and holoprosencephaly in only one monozygotic twin. Author(s): Reinecke P, Figge C, Majewski F, Borchard F. Source: American Journal of Medical Genetics. 2003 June 15; 119A(3): 395-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12784314

•

Palate structure in human holoprosencephaly correlates with the facial malformation and demonstrates a new palatal developmental field. Author(s): Kjaer I, Keeling J, Russell B, Daugaard-Jensen J, Fischer Hansen B. Source: American Journal of Medical Genetics. 1997 December 31; 73(4): 387-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9415463

•

Partial deletions of the long arm of chromosome 13 associated with holoprosencephaly and the Dandy-Walker malformation. Author(s): McCormack WM Jr, Shen JJ, Curry SM, Berend SA, Kashork C, Pinar H, Potocki L, Bejjani BA. Source: American Journal of Medical Genetics. 2003 April 15; 118A(2): 384-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12698964

52

Holoprosencephaly

•

Partial deletions of the long arm of chromosome 13 associated with holoprosencephaly and the Dandy-Walker malformation. Author(s): McCormack WM Jr, Shen JJ, Curry SM, Berend SA, Kashork C, Pinar H, Potocki L, Bejjani BA. Source: American Journal of Medical Genetics. 2002 November 1; 112(4): 384-9. Corrected and Republished In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12376941

•

Perspectives on holoprosencephaly: Part I. Epidemiology, genetics, and syndromology. Author(s): Cohen MM Jr. Source: Teratology. 1989 September; 40(3): 211-35. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2688166

•

Perspectives on holoprosencephaly: Part II. Central nervous system, craniofacial anatomy, syndrome commentary, diagnostic approach, and experimental studies. Author(s): Cohen MM Jr, Sulik KK. Source: Journal of Craniofacial Genetics and Developmental Biology. 1992 OctoberDecember; 12(4): 196-244. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1494025

•

Perspectives on holoprosencephaly: Part III. Spectra, distinctions, continuities, and discontinuities. Author(s): Cohen MM Jr. Source: American Journal of Medical Genetics. 1989 October; 34(2): 271-88. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2683788

•

Physical mapping of the holoprosencephaly critical region in 18p11.3. Author(s): Overhauser J, Mitchell HF, Zackai EH, Tick DB, Rojas K, Muenke M. Source: American Journal of Human Genetics. 1995 November; 57(5): 1080-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7485158

•

Physical mapping of the holoprosencephaly critical region in 21q22.3, exclusion of SIM2 as a candidate gene for holoprosencephaly, and mapping of SIM2 to a region of chromosome 21 important for Down syndrome. Author(s): Muenke M, Bone LJ, Mitchell HF, Hart I, Walton K, Hall-Johnson K, Ippel EF, Dietz-Band J, Kvaloy K, Fan CM, et al. Source: American Journal of Human Genetics. 1995 November; 57(5): 1074-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7485157

Studies

53

•

Physical mapping of the holoprosencephaly critical region on chromosome 7q36. Author(s): Gurrieri F, Trask BJ, van den Engh G, Krauss CM, Schinzel A, Pettenati MJ, Schindler D, Dietz-Band J, Vergnaud G, Scherer SW, et al. Source: Nature Genetics. 1993 March; 3(3): 247-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8485580

•

Preimplantation diagnosis for sonic hedgehog mutation causing familial holoprosencephaly. Author(s): Verlinsky Y, Rechitsky S, Verlinsky O, Ozen S, Sharapova T, Masciangelo C, Morris R, Kuliev A. Source: The New England Journal of Medicine. 2003 April 10; 348(15): 1449-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12686701

•

Prenatal diagnosis by ultrasound of midface defects associated with holoprosencephaly. Author(s): Toth Z, Csecsei K, Szeifert GT, Papp Z. Source: Acta Chir Hung. 1988; 29(3): 215-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3071057

•

Prenatal diagnosis of 13q- syndrome in a fetus with holoprosencephaly and thumb agenesis. Author(s): Gutierrez J, Sepulveda W, Saez R, Carstens E, Sanchez J. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2001 February; 17(2): 166-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11320988

•

Prenatal diagnosis of agnathia-holoprosencephaly: three-dimensional imaging by helical computed tomography. Author(s): Ebina Y, Yamada H, Kato EH, Tanuma F, Shimada S, Cho K, Fujimoto S. Source: Prenatal Diagnosis. 2001 January; 21(1): 68-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11180246

•

Prenatal diagnosis of alobar holoprosencephaly at 10 weeks of gestation. Author(s): Turner CD, Silva S, Jeanty P. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 1999 May; 13(5): 360-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10380303

•

Prenatal diagnosis of alobar holoprosencephaly by two-dimensional and threedimensional ultrasound. Author(s): Lai TH, Chang CH, Yu CH, Kuo PL, Chang FM. Source: Prenatal Diagnosis. 2000 May; 20(5): 400-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10820408

54

Holoprosencephaly

•

Prenatal diagnosis of de novo isochromosome 13q associated with microcephaly, alobar holoprosencephaly and cebocephaly in a fetus. Author(s): Chen CP, Chern SR, Lee CC, Chen LF, Chuang CY, Chen MH. Source: Prenatal Diagnosis. 1998 April; 18(4): 393-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9602489

•

Prenatal diagnosis of holoprosencephaly (HPE) in a fetus with a recombinant (18)dup(18q)inv(18)(p11.31q11.2)mat. Author(s): Leonard NJ, Tomkins DJ, Demianczuk N. Source: Prenatal Diagnosis. 2000 December; 20(12): 947-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11113905

•

Prenatal diagnosis of holoprosencephaly and ectopia cordis in a twin at 12 weeks' gestation. Author(s): Taipale PJ, Krista T, Alafuzoff I. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2003 February; 21(2): 198-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12601848

•

Prenatal diagnosis of holoprosencephaly in two fetuses with der (7)t(1;7)(q32;q32)pat inherited from the father with double translocations. Author(s): Chuang L, Kuo PL, Yang HB, Chien CH, Chen PY, Chang CH, Chang FM. Source: Prenatal Diagnosis. 2003 February; 23(2): 134-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12575020

•

Prenatal diagnosis of iniencephaly and alobar holoprosencephaly with trisomy 13 mosaicism: a case report. Author(s): Phadke SR, Thakur S. Source: Prenatal Diagnosis. 2002 December; 22(13): 1240-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12478643

•

Prenatal diagnosis of partial monosomy 18p(18p11.2-->pter) and trisomy 21q(21q22.3->qter) with alobar holoprosencephaly and premaxillary agenesis. Author(s): Chen CP, Chern SR, Wang W, Lee CC, Chen WL, Chen LF, Chang TY, Tzen CY. Source: Prenatal Diagnosis. 2001 May; 21(5): 346-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11360273

Studies

55

•

Prenatal diagnosis of partial trisomy 3p(3p23-->pter) and monosomy 7q(7q36-->qter) in a fetus with microcephaly alobar holoprosencephaly and cyclopia. Author(s): Chen CP, Devriendt K, Lee CC, Chen WL, Wang W, Wang TY. Source: Prenatal Diagnosis. 1999 October; 19(10): 986-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10521829

•

Prenatal diagnosis of terminal deletion 7q and partial trisomy 3p in fetuses with holoprosencephaly. Author(s): Chen CP, Liu FF, Jan SW, Lin CL, Lan CC. Source: Clinical Genetics. 1996 November; 50(5): 321-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9007318

•

Prenatal sonographic diagnosis of holoprosencephaly. Author(s): Tongsong T, Wanapirak C, Sirichotiyakul S, Siriangkul S. Source: J Med Assoc Thai. 1998 March; 81(3): 208-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9623013

•

Prenatal sonographic diagnosis of median facial cleft should alert holoprosencephaly with premaxillary agenesis and prompt genetic investigations. Author(s): Chen CP. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2002 April; 19(4): 421-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11952980

•

Previously undescribed nonsense mutation in SHH caused autosomal dominant holoprosencephaly with wide intrafamilial variability. Author(s): Marini M, Cusano R, De Biasio P, Caroli F, Lerone M, Silengo M, Ravazzolo R, Seri M, Camera G. Source: American Journal of Medical Genetics. 2003 March 1; 117A(2): 112-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12567406

•

Problems in the definition of holoprosencephaly. Author(s): Cohen MM Jr. Source: American Journal of Medical Genetics. 2001 October 15; 103(3): 183-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11745988

•

Prolonged survival and childhood-onset epilepsy in alobar holoprosencephaly. Author(s): Plawner L, Clegg N, Kinsman S, Delgado M. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2000 April; 16(4): 195. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10855513

56

Holoprosencephaly

•

Pseudotrisomy 13 and autosomal recessive holoprosencephaly. Author(s): Seller MJ, Chitty LS, Dunbar H. Source: Journal of Medical Genetics. 1993 November; 30(11): 970-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8301659

•

Psychosis associated with lobar holoprosencephaly. Author(s): Hercig D, Bau A, Reznek L. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1994 September; 39(7): 449. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7987790

•

Radiological features of holoprosencephaly. Author(s): Hayashi T, Yoshida M, Kuramoto S, Takeya S, Hashimoto T. Source: Surgical Neurology. 1979 September; 12(3): 261-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=515929

•

Radiologic-pathologic correlation. Alobar holoprosencephaly. Author(s): Castillo M, Bouldin TW, Scatliff JH, Suzuki K. Source: Ajnr. American Journal of Neuroradiology. 1993 September-October; 14(5): 11516. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8237694

•

Recurrence of holoprosencephaly in families with a positive history. Author(s): Benke PJ, Cohen MM Jr. Source: Clinical Genetics. 1983 November; 24(5): 324-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6652942

•

Recurrent bradycardia and delayed recovery in a neonate following repair of nasofrontal encephalocoele with holoprosencephaly and single cerebral ventricle. Author(s): Bharti N, Dash HH, Mahapatra AK. Source: Journal of Neurosurgical Anesthesiology. 2003 April; 15(2): 140-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12658000

•

Reliable criteria for the prenatal sonographic diagnosis of alobar holoprosencephaly. Author(s): Greene MF, Benacerraf BR, Frigoletto FD Jr. Source: American Journal of Obstetrics and Gynecology. 1987 March; 156(3): 687-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3548385

•

Retinoblastoma associated with holoprosencephaly. Author(s): Desai VN, Shields CL, Shields JA, Donoso LA, Wagner RS. Source: American Journal of Ophthalmology. 1990 March 15; 109(3): 355-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2309872

Studies

57

•

Retroflexion of holoprosencephaly: report of two cases. Author(s): Kitanaka C, Iwasaki Y, Yamada H. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1992 September; 8(6): 317-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1394278

•

Risk factors for cytogenetically normal holoprosencephaly in California: a population-based case-control study. Author(s): Croen LA, Shaw GM, Lammer EJ. Source: American Journal of Medical Genetics. 2000 February 14; 90(4): 320-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10710231

•

Roentgenology of holoprosencephaly (arhinencephaly). Author(s): Kurlander GJ, DeMyer W, Campbell JA, Taybi H. Source: Acta Radiol Diagn (Stockh). 1966; 5: 25-40. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5957829

•

Segregation analysis in nonsyndromic holoprosencephaly. Author(s): Odent S, Le Marec B, Munnich A, Le Merrer M, Bonaiti-Pellie C. Source: American Journal of Medical Genetics. 1998 May 1; 77(2): 139-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9605287

•

Semilobar holoprosencephaly diagnosed by MRI. Author(s): Mortelmans ES, Van Goethem JW, van den Hauwe L, Parizel PM, De Schepper AM. Source: Jbr-Btr. 2002 June-July; 85(3): 144-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12152724

•

Semilobar holoprosencephaly in a 46,XY female fetus. Author(s): Witters I, Moerman P, Muenke M, Van Assche FA, Devriendt K, Legius E, Van Schoubroeck D, Fryns JP. Source: Prenatal Diagnosis. 2001 October; 21(10): 839-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11746125

•

Semilobar holoprosencephaly with associated Arnold-Chiari variant. Author(s): Britton CA. Source: Journal of Clinical Ultrasound : Jcu. 1989 June; 17(5): 374-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2499604

58

Holoprosencephaly

•

Semilobar holoprosencephaly with midline 'seam': a topologic and morphogenetic model based upon MRI analysis. Author(s): Takahashi T, Kinsman S, Makris N, Grant E, Haselgrove C, McInerney S, Kennedy DN, Takahashi T, Fredrickson K, Mori S, Caviness VS. Source: Cerebral Cortex (New York, N.Y. : 1991). 2003 December; 13(12): 1299-312. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14615296

•

Semilobar holoprosencephaly, coronal craniosynostosis, and multiple congenital anomalies: a severe expression of the Genoa syndrome or a newly recognized syndrome? Author(s): Lapunzina P, Musante G, Pedraza A, Prudent L, Gadow E. Source: American Journal of Medical Genetics. 2001 August 15; 102(3): 258-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11484203

•

Semilobar holoprosencephaly: embryologic, CSF dynamics and radiological considerations. Author(s): Gangemi M, Maiuri F, Tajana GF, Maiuri L. Source: Acta Neurol (Napoli). 1986 February; 8(1): 13-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3962751

•

Single central incisor in familial holoprosencephaly. Author(s): Berry SA, Pierpont ME, Gorlin RJ. Source: The Journal of Pediatrics. 1984 June; 104(6): 877-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6726520

•

Single central maxillary incisor and holoprosencephaly. Author(s): Fryns JP, Van den Berghe H. Source: American Journal of Medical Genetics. 1988 August; 30(4): 943-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3189415

•

Single central maxillary incisor and holoprosencephaly. Author(s): Hattori H, Okuno T, Momoi T, Kataoka K, Mikawa H, Shiota K. Source: American Journal of Medical Genetics. 1987 October; 28(2): 483-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3425622

•

Single stage repair of the median cleft lip deformity in holoprosencephaly. Author(s): Voy ED. Source: Journal of Cranio-Maxillo-Facial Surgery : Official Publication of the European Association for Cranio-Maxillo-Facial Surgery. 1990 May; 18(4): 182-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2358509

Studies

59

•

Single stage repair of the median cleft lip deformity in holoprosencephaly. Author(s): Sadove AM, Eppley BL, DeMyer W. Source: Journal of Cranio-Maxillo-Facial Surgery : Official Publication of the European Association for Cranio-Maxillo-Facial Surgery. 1989 November; 17(8): 363-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2592577

•

Single-stage lip and nasal reconstruction in holoprosencephaly. Author(s): Taub PJ, Bradley JP, Markowitz BL. Source: Plastic and Reconstructive Surgery. 2003 June; 111(7): 2324-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12794475

•

Skewed sex ratios in familial holoprosencephaly and in people with isolated single maxillary central incisor. Author(s): Suthers G, Smith S, Springbett S. Source: Journal of Medical Genetics. 1999 December; 36(12): 924-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10594002

•

Smith-Lemli-Opitz (RHS) syndrome: holoprosencephaly and homozygous IVS8-1G->C genotype. Author(s): Nowaczyk MJ, Farrell SA, Sirkin WL, Velsher L, Krakowiak PA, Waye JS, Porter FD. Source: American Journal of Medical Genetics. 2001 September 15; 103(1): 75-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11562938

•

SONIC HEDGEHOG mutations causing human holoprosencephaly impair neural patterning activity. Author(s): Schell-Apacik C, Rivero M, Knepper JL, Roessler E, Muenke M, Ming JE. Source: Human Genetics. 2003 July; 113(2): 170-7. Epub 2003 April 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12709790

•

Sonic hedgehog signal peptide mutation in a patient with holoprosencephaly. Author(s): Kato M, Nanba E, Akaboshi S, Shiihara T, Ito A, Honma T, Tsuburaya K, Hayasaka K. Source: Annals of Neurology. 2000 April; 47(4): 514-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10762164

•

Sonography of facial features of alobar and semilobar holoprosencephaly. Author(s): McGahan JP, Nyberg DA, Mack LA. Source: Ajr. American Journal of Roentgenology. 1990 January; 154(1): 143-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2104699

60

Holoprosencephaly

•

Structure of the human Lanosterol synthase gene and its analysis as a candidate for holoprosencephaly (HPE1). Author(s): Roessler E, Mittaz L, Du Y, Scott HS, Chang J, Rossier C, Guipponi M, Matsuda SP, Muenke M, Antonarakis SE. Source: Human Genetics. 1999 November; 105(5): 489-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10598817

•

Sub-band deletion of 7q36.3 in a patient with ring chromosome 7: association with holoprosencephaly. Author(s): Sawyer JR, Lukacs JL, Hassed SJ, Arnold GL, Mitchell HF, Muenke M. Source: American Journal of Medical Genetics. 1996 October 16; 65(2): 113-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8911601

•

Sublingual administration of desmopressin. Effectiveness in an infant with holoprosencephaly and central diabetes insipidus. Author(s): Kappy MS, Sonderer E. Source: Am J Dis Child. 1987 January; 141(1): 84-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3788888

•

Surgical treatment of patients with lobar holoprosencephaly: a personal note. Author(s): Pensler JM, Giese S, Charrow J. Source: The Journal of Craniofacial Surgery. 1993 January; 4(1): 2-5; Discussion 6-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8467017

•

Syndromal hypothalamic hamartoblastoma with holoprosencephaly sequence, microphthalmia, pulmonary malformations, radial hypoplasia and mullerian regression: further delineation of a new syndrome? Author(s): Verloes A, Narcy F, Fallet-Bianco C. Source: Clinical Dysmorphology. 1995 January; 4(1): 33-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7735503

•

Synophthalmia and holoprosencephaly in chromosome 18p deletion defect. Author(s): Kuchle M, Kraus J, Rummelt C, Naumann GO. Source: Archives of Ophthalmology. 1991 January; 109(1): 136-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1987932

•

Temporary arrest of fetal movement with pancuronium bromide to enable antenatal magnetic resonance imaging of holoprosencephaly. Author(s): Horvath L, Seeds JW. Source: American Journal of Perinatology. 1989 October; 6(4): 418-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2789538

Studies

61

•

Teratogenesis of holoprosencephaly. Author(s): Cohen MM Jr, Shiota K. Source: American Journal of Medical Genetics. 2002 April 15; 109(1): 1-15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11932986

•

Terminal 7q deletion as a cause of holoprosencephaly. Author(s): Masuno M, Orii T. Source: Clinical Genetics. 1990 March; 37(3): 238. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2323097

•

The decision to continue: the experiences and needs of parents who receive a prenatal diagnosis of holoprosencephaly. Author(s): Am J Med Genet. 2003 Apr 15;118A(2):384-9 Source: American Journal of Medical Genetics. 2002 November 1; 112(4): 369-78. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12698964

•

The development of the corpus callosum in semilobar and lobar holoprosencephaly. Author(s): Rubinstein D, Cajade-Law AG, Youngman V, Hise JM, Baganz M. Source: Pediatric Radiology. 1996 December; 26(12): 839-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8929294

•

The dorsal cyst in holoprosencephaly and the role of the thalamus in its formation. Author(s): Simon EM, Hevner RF, Pinter J, Clegg NJ, Delgado M, Kinsman SL, Hahn JS, Barkovich AJ. Source: Neuroradiology. 2001 September; 43(9): 787-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11594433

•

The dup(3)(p25 leads to pter) syndrome: a case with holoprosencephaly. Author(s): Martin NJ, Steinberg BG. Source: American Journal of Medical Genetics. 1983 April; 14(4): 767-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6846406

•

The facial features of holoprosencephaly in anencephalic human specimens. I. Historical review and associated malformations. Author(s): Lemire RJ, Cohen MM Jr, Beckwith JB, Kokich VG, Siebert JR. Source: Teratology. 1981 June; 23(3): 297-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7256655

62

Holoprosencephaly

•

The facial features of holoprosencephaly in anencephalic human specimens. II. Craniofacial anatomy. Author(s): Siebert JR, Kokich VG, Beckwith JB, Cohen MM Jr, Lemire RJ. Source: Teratology. 1981 June; 23(3): 305-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7256656

•

The genomic structure, chromosomal localization, and analysis of SIL as a candidate gene for holoprosencephaly. Author(s): Karkera JD, Izraeli S, Roessler E, Dutra A, Kirsch I, Muenke M. Source: Cytogenetic and Genome Research. 2002; 97(1-2): 62-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12438740

•

The genomic structure, chromosome location, and analysis of the human DKK1 head inducer gene as a candidate for holoprosencephaly. Author(s): Roessler E, Du Y, Glinka A, Dutra A, Niehrs C, Muenke M. Source: Cytogenetics and Cell Genetics. 2000; 89(3-4): 220-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10965128

•

The interplay of genetic and environmental factors in craniofacial morphogenesis: holoprosencephaly and the role of cholesterol. Author(s): Edison R, Muenke M. Source: Congenit Anom (Kyoto). 2003 March; 43(1): 1-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12692399

•

The middle interhemispheric variant of holoprosencephaly. Author(s): Simon EM, Hevner RF, Pinter JD, Clegg NJ, Delgado M, Kinsman SL, Hahn JS, Barkovich AJ. Source: Ajnr. American Journal of Neuroradiology. 2002 January; 23(1): 151-6. Erratum In: Ajnr Am J Neuroradiol 2002 April; 23(4): 742. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11827888

•

The molecular genetics of holoprosencephaly: a model of brain development for the next century. Author(s): Roessler E, Muenke M. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1999 November; 15(11-12): 646-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10603005

Studies

63

•

The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly. Author(s): Nanni L, Ming JE, Bocian M, Steinhaus K, Bianchi DW, Die-Smulders C, Giannotti A, Imaizumi K, Jones KL, Campo MD, Martin RA, Meinecke P, Pierpont ME, Robin NH, Young ID, Roessler E, Muenke M. Source: Human Molecular Genetics. 1999 December; 8(13): 2479-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10556296

•

The obstetric significance of holoprosencephaly. Author(s): Chervenak FA, Isaacson G, Mahoney MJ, Tortora M, Mesologites T, Hobbins JC. Source: Obstetrics and Gynecology. 1984 January; 63(1): 115-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6691008

•

The search for genes that cause holoprosencephaly: possible approaches. Author(s): Gurrieri F, Muenke M. Source: Birth Defects Orig Artic Ser. 1996; 30(1): 247-50. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9125331

•

The sixth clinical report of a rare association: agnathia-holoprosencephaly-situs inversus. Author(s): Ozden S, Bilgic R, Delikara N, Basaran T. Source: Prenatal Diagnosis. 2002 September; 22(9): 840-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12224086

•

The visual evoked potential in neonates with occipital lesions and holoprosencephaly. Author(s): Mushin J, Dubowitz LM, De Vries L, Arden GB. Source: Behavioural Brain Research. 1986 August; 21(2): 79-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3530278

•

Towards a greater understanding of the pathogenesis of holoprosencephaly. Author(s): Golden JA. Source: Brain & Development. 1999 December; 21(8): 513-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10598051

•

Translocation 1q15q in a fetus with holoprosencephaly. Author(s): Leite RP, Carvalho A, Ribeiro E. Source: Prenatal Diagnosis. 2002 December; 22(13): 1238-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12478641

64

Holoprosencephaly

•

Transverse limb defects, holoprosencephaly and neuronal heterotopia--a new syndrome? Author(s): Slavotinek A, Stahlschmidt J, Moore L. Source: Clinical Dysmorphology. 1997 October; 6(4): 365-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9354847

•

Trilobar holoprosencephaly ("triprosencephaly"): a unique type of cerebral malformation. Author(s): Mazal PR, Schuhfried G, Budka H. Source: Acta Neuropathologica. 1995; 89(6): 567-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7676813

•

Trisomy 22 with holoprosencephaly: a clinicopathologic study. Author(s): Isada NB, Bolan JC, Larsen JW Jr, Kent SG. Source: Teratology. 1990 October; 42(4): 333-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2255998

•

Ultrasonic findings with holoprosencephaly. Author(s): Hill LM, Breckle R, Bonebrake CR. Source: J Reprod Med. 1982 March; 27(3): 172-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7086766

•

Ultrasound case study of holoprosencephaly. Author(s): Clewes JS, Lewin E. Source: Radiogr Today. 1988 December; 54(619): 42-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3077600

•

Unknown syndrome: holoprosencephaly, congenital heart defects, and polydactyly. Author(s): Young ID, Madders DJ. Source: Journal of Medical Genetics. 1987 November; 24(11): 714-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3430550

•

Unusual variant of holoprosencephaly in monosomy 13q. Author(s): Marcorelles P, Loget P, Fallet-Bianco C, Roume J, Encha-Razavi F, Delezoide AL. Source: Pediatric and Developmental Pathology : the Official Journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 2002 March-April; 5(2): 170-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11910512

Studies

65

•

Unusually prolonged survival and childhood-onset epilepsy in a case of alobar holoprosencephaly. Author(s): Veneselli E, Biancheri R, Di Rocco M, Fondelli MP, Perrone MV, Donati PT. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1999 May; 15(5): 274-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10392502

•

Velo-cardio-facial syndrome presenting as holoprosencephaly. Author(s): Wraith JE, Super M, Watson GH, Phillips M. Source: Clinical Genetics. 1985 April; 27(4): 408-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3995791

•

What is the incidence of holoprosencephaly? Author(s): Saunders ES, Shortland D, Dunn PM. Source: Journal of Medical Genetics. 1984 February; 21(1): 21-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6694181

67

CHAPTER 2. NUTRITION AND HOLOPROSENCEPHALY Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and holoprosencephaly.

Finding Nutrition Studies on Holoprosencephaly The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.4 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “holoprosencephaly” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

4 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

68

Holoprosencephaly

The following information is typical of that found when using the “Full IBIDS Database” to search for “holoprosencephaly” (or a synonym): •

Association between holoprosencephaly and exposure to topical retinoids: results of the EUROCAT Survey. Author(s): EUROCAT Central Registry, Department of Epidemiology, Catholic University of Louvain, Brussels, Belgium. Source: De Wals, P Bloch, D Calabro, A Calzolari, E Cornel, M C Johnson, Z Ligutic, I Nevin, N Pexieder, I Stoll, C et al. Paediatr-Perinat-Epidemiol. 1991 October; 5(4): 445-7 0269-5022

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

•

The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

•

The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

•

The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

•

The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

•

Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

•

Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

•

Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

•

Google: http://directory.google.com/Top/Health/Nutrition/

•

Healthnotes: http://www.healthnotes.com/

•

Open Directory Project: http://dmoz.org/Health/Nutrition/

Nutrition

•

Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

•

WebMDHealth: http://my.webmd.com/nutrition

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

69

71

CHAPTER 3. ALTERNATIVE MEDICINE AND HOLOPROSENCEPHALY Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to holoprosencephaly. 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 holoprosencephaly 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 “holoprosencephaly” (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 holoprosencephaly: •

Hydrocephalus manifestation in the genetic polydactyly/ arhinencephaly mouse (Pdn/Pdn). Author(s): Naruse I, Ueta E. Source: Congenit Anom (Kyoto). 2002 March; 42(1): 27-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12094077

•

The evolution of neurophysiological features in holoprosencephaly. Author(s): Watanabe K, Hara K, Iwase K. Source: Neuropadiatrie. 1976 February; 7(1): 19-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=988915

•

Treatment of the West syndrome with high-dose pyridoxal phosphate. Author(s): Ohtsuka Y, Matsuda M, Ogino T, Kobayashi K, Ohtahara S.

72

Holoprosencephaly

Source: Brain & Development. 1987; 9(4): 418-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3434717

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/

•

AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

•

Chinese Medicine: http://www.newcenturynutrition.com/

•

drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

•

Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

•

Google: http://directory.google.com/Top/Health/Alternative/

•

Healthnotes: http://www.healthnotes.com/

•

MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

•

Open Directory Project: http://dmoz.org/Health/Alternative/

•

HealthGate: http://www.tnp.com/

•

WebMDHealth: http://my.webmd.com/drugs_and_herbs

•

WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

•

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.

73

CHAPTER 4. BOOKS ON HOLOPROSENCEPHALY Overview This chapter provides bibliographic book references relating to holoprosencephaly. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on holoprosencephaly include the Combined Health Information Database and the National Library of Medicine. 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 “holoprosencephaly” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “holoprosencephaly” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “holoprosencephaly” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

The Official Parent's Sourcebook on Holoprosencephaly by Icon Health Publications; ISBN: 0597834962; http://www.amazon.com/exec/obidos/ASIN/0597834962/icongroupinterna

Chapters on Holoprosencephaly In order to find chapters that specifically relate to holoprosencephaly, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and holoprosencephaly using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type

74

Holoprosencephaly

“holoprosencephaly” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on holoprosencephaly: •

Complex Craniofacial Disorders Source: in Gerber, S.E. Etiology and Prevention of Communicative Disorders. 2nd ed. San Diego, CA: Singular Publishing Group, Inc. 1998. p. 147-199. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545 or (619) 238-6777. Fax (800) 774-8398 or (619) 238-6789. E-mail: [email protected]. Website: www.singpub.com. PRICE: $65.00 plus shipping and handling. ISBN: 1565939476. Summary: This chapter on complex craniofacial disorders is from a textbook that focuses on the primary and secondary prevention of communicative disorders. This chapter provides a conceptual framework regarding the relationship of communicative impairment to congenital anomalies of the craniofacial complex. The author first discusses insight and prediction, including the phenotypic spectrum, natural history, and prognosis. Topics include achondroplasia syndrome, amnion disruptions (ADAM) sequence, Apert syndrome, arthrogryposis, Beckwith Wiedemann syndrome, bilateral femoral dysgenesis unusual facies syndrome, Carpenter syndrome, CHARGE association, chromosomal syndromes, clefting and oral teratoma syndrome, cleidocranial dysplasia syndrome, Cornelia de Lange syndrome, craniofrontonasal dysplasia syndrome, craniometaphyseal dysplasia, diatrophic dysplasia syndrome, EEC (ectrodactyly ectodermal dysplasia clefting) syndrome, fetal alcohol effects, fetal hydantoin effects, Freeman Sheldon syndrome, G syndrome (Opitz Frias syndrome), hemifacial microsomia, holoprosencephaly sequence, hypoglossia hypodactyly syndrome, Kniest syndrome, Larsen syndrome, LEOPARD syndrome, lysosomal storage syndrome, Miller Diecker syndrome, multiple synostosis syndrome, Nager syndrome, neurofibromatosis, Noonan syndrome, oral facial digital (OFD) syndromes, otopalatodigital syndrome, Pfeiffer syndrome, popliteal pterygium syndrome, Prader Willi syndrome, Rapp Hodgkin syndrome, Robin deformation sequence, Robinow syndrome, Rubinstein Taybi syndrome, Saethre Chotzen syndrome, Shprintzen Goldberg syndrome (I and II), Sotos syndrome, spondyloepiphyseal dysplasia syndrome, Steinert syndrome, Stickler syndrome, Townes syndrome, Treacher Collins syndrome, Turner syndrome, Van der Woude syndrome, velocardiofacial syndrome, Waardenburg syndrome, Weaver syndrome, and Williams syndrome. The chapter concludes with a glossary of terms and a reference list. 34 figures. 35 references.

75

CHAPTER 5. PERIODICALS AND NEWS ON HOLOPROSENCEPHALY Overview In this chapter, we suggest a number of news sources and present various periodicals that cover holoprosencephaly.

News Services and Press Releases One of the simplest ways of tracking press releases on holoprosencephaly is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “holoprosencephaly” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to holoprosencephaly. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “holoprosencephaly” (or synonyms).

76

Holoprosencephaly

The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “holoprosencephaly” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “holoprosencephaly” (or synonyms). If you know the name of a company that is relevant to holoprosencephaly, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “holoprosencephaly” (or synonyms).

Periodicals and News

77

Academic Periodicals covering Holoprosencephaly Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to holoprosencephaly. In addition to these sources, you can search for articles covering holoprosencephaly that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

79

APPENDICES

81

APPENDIX A. 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 Institute5: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

5

These publications are typically written by one or more of the various NIH Institutes.

82

Holoprosencephaly

•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

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

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

Physician Resources

83

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.6 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 citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:7 •

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

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

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/hmd.html

•

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/

•

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

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

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/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

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

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

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

6

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). 7 See http://www.nlm.nih.gov/databases/databases.html.

84

Holoprosencephaly

•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

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

The NLM Gateway8 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.9 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “holoprosencephaly” (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 1118 3 23 0 60 1204

HSTAT10 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.11 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.12 Simply search by “holoprosencephaly” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

8

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

9

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). 10 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 11 12

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.

Physician Resources

85

Coffee Break: Tutorials for Biologists13 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. 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.14 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.15 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: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

13 Adapted 14

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

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. 15 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.

87

APPENDIX B. 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 holoprosencephaly 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 The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to holoprosencephaly. 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 holoprosencephaly. 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 “holoprosencephaly”:

88

Holoprosencephaly

Birth Defects http://www.nlm.nih.gov/medlineplus/birthdefects.html Facial Injuries and Disorders http://www.nlm.nih.gov/medlineplus/facialinjuriesanddisorders.html Genetic Brain Disorders http://www.nlm.nih.gov/medlineplus/geneticbraindisorders.html Head and Brain Malformations http://www.nlm.nih.gov/medlineplus/headandbrainmalformations.html Neural Tube Defects http://www.nlm.nih.gov/medlineplus/neuraltubedefects.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. 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 holoprosencephaly. 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://search.nih.gov/index.html. NORD (The National Organization of Rare Disorders, Inc.) NORD provides an invaluable service to the public by publishing short yet comprehensive guidelines on over 1,000 diseases. NORD primarily focuses on rare diseases that might not be covered by the previously listed sources. NORD’s Web address is http://www.rarediseases.org/. A complete guide on holoprosencephaly can be purchased from NORD for a nominal fee. PEDBASE Similar to NORD, PEDBASE covers relatively rare disorders, limited mainly to pediatric conditions. PEDBASE was designed by Dr. Alan Gandy. To access the database, which is more oriented to researchers than patients, you can view the current list of health topics covered at the following Web site: http://www.icondata.com/health/pedbase/pedlynx.htm.

Patient Resources

89

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: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Associations and Holoprosencephaly The following is a list of associations that provide information on and resources relating to holoprosencephaly: •

Carter Centers for Brain Research in Holoprosencephaly and RelatedMalformations Telephone: (214) 559-8411 Toll-free: (800) 421-1121 Fax: (214) 559-8383 Email: [email protected] Web Site: http://www.stanford.edu/group/hpe Background: The Carter Centers for Brain Research in Holoprosencephaly represent the most concentrated study of holoprosencephaly in the world. The Centers were created to gather, store, organize, analyze and share information about HPE, but most importantly, to help families find hope. Holoprosencephaly (HPE) is a neurological birth defect in which the fetal brain does not grow and divide as it should during early pregnancy. The effects of this brain malformation can range from mild to severe. Specific chromosomal abnormalities and gene mutations have been identified in some patients and there is evidence that in some families, HPE is inherited. The Carter Centers are a collaborative initiative among sponsored Centers of Excellence in the field of HPE: The Texas Scottish Rite Hospital for Children in Texas; the Kennedy Krieger Institute in Maryland; Stanford University and UCSF in California; and National Institutes of Health in Maryland. Relevant area(s) of interest: Arhinencephaly, Holoprosencephaly

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to holoprosencephaly. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with holoprosencephaly.

90

Holoprosencephaly

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 holoprosencephaly. 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. 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://www.sis.nlm.nih.gov/Dir/DirMain.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. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “holoprosencephaly” (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://www.sis.nlm.nih.gov/hotlines/. 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 Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “holoprosencephaly”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “holoprosencephaly” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. 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 “holoprosencephaly” (or a synonym) into the search box, and click “Submit Query.”

91

APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.16

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

16

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

92

Holoprosencephaly

libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)17: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

17

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

93

•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

94

Holoprosencephaly

•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries

95

•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

•

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

•

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

96

Holoprosencephaly

•

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

97

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

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

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

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

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).

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

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

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

99

HOLOPROSENCEPHALY DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Acylation: The addition of an organic acid radical into a molecule. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Agenesis: Lack of complete or normal development; congenital absence of an organ or part. [NIH]

Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [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: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] 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] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid.

100

Holoprosencephaly

[NIH]

Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [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] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Aniridia: A congenital abnormality in which there is only a rudimentary iris. This is due to the failure of the optic cup to grow. Aniridia also occurs in a hereditary form, usually autosomal dominant. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anophthalmia: Absence of an eye or eyes in the newborn due to failure of development of the optic cup or to disappearance of the eyes after partial development. [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] Antidiuretic: Suppressing the rate of urine formation. [EU] 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

Dictionary 101

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] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Aplasia: Lack of development of an organ or tissue, or of the cellular products from an organ or tissue. [EU] Aqueous: Having to do with water. [NIH] Argipressin: Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly-NH2, cyclic 1-6 disulfide. The usual mammalian antidiuretic hormone, it is a cyclic nonapeptide with arginine in position 8 of the chain. Argipressin is used to treat diabetes insipidus and as hemostatic because of its vasoconstrictor action. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] 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] 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] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [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] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriophage lambda: A temperate inducible phage and type species of the genus lambdalike Phages, in the family Siphoviridae. Its natural host is E. coli K12. Its virion contains linear double-stranded DNA, except for 12 complementary bases at the 5'-termini of the

102

Holoprosencephaly

polynucleotide chains. The DNA circularizes on infection. [NIH] Basal cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benign tumor: A noncancerous growth that does not invade nearby tissue or spread to other parts of the body. [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] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [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] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] 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] Bladder: The organ that stores urine. [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] 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] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Bradycardia: Excessive slowness in the action of the heart, usually with a heart rate below 60 beats per minute. [NIH]

Dictionary 103

Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [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] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [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] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Carbohydrates: The largest class of organic compounds, including starches, glycogens, cellulose, gums, and simple sugars. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. [NIH] Carboxy: Cannabinoid. [NIH] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [NIH]

Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]

Cardiovascular: Having to do with the heart and blood vessels. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [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] Cataracts: In medicine, an opacity of the crystalline lens of the eye obstructing partially or totally its transmission of light. [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] Causality: The relating of causes to the effects they produce. Causes are termed necessary when they must always precede an effect and sufficient when they initiate or produce an effect. Any of several factors may be associated with the potential disease causation or outcome, including predisposing factors, enabling factors, precipitating factors, reinforcing factors, and risk factors. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are

104

Holoprosencephaly

made up of one or more 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 proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] 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 man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] 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] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [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] Choanal Atresia: Congenital bony or membranous occlusion of one or both choanae, due to failure of the embryonic bucconasal membrane to rupture. [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] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is

Dictionary 105

also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [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 Abnormalities: Defects in the structure or number of chromosomes resulting in structural aberrations or manifesting as disease. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [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] Cleft Lip: Congenital defect in the upper lip where the maxillary prominence fails to merge with the merged medial nasal prominences. It is thought to be caused by faulty migration of the mesoderm in the head region. [NIH] Cleft Palate: Congenital fissure of the soft and/or hard palate, due to faulty fusion. [NIH] 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] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Coloboma: Congenital anomaly in which some of the structures of the eye are absent due to incomplete fusion of the fetal intraocular fissure during gestation. [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [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

106

Holoprosencephaly

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, 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] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU]

Dictionary 107

Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Congenita: Displacement, subluxation, or malposition of the crystalline lens. [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] 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] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] 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 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] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Craniofacial Abnormalities: Congenital structural deformities, malformations, or other

108

Holoprosencephaly

abnormalities of the cranium and facial bones. [NIH] Criterion: A standard by which something may be judged. [EU] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclopia: Elements of the two eyes fused into one median eye in the center of the forehead of a fetal monster. [NIH] Cyst: A sac or capsule filled with fluid. [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] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]

Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Defective Viruses: Viruses which lack a complete genome so that they cannot completely replicate or cannot form a protein coat. Some are host-dependent defectives, meaning they can replicate only in cell systems which provide the particular genetic function which they lack. Others, called satellite viruses, are able to replicate only when their genetic defect is complemented by a helper virus. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dermal: Pertaining to or coming from the skin. [NIH] Desmopressin: A synthetic analog of the natural hormone 8-arginine vasopressin (argipressin). Its action is mediated by the vasopressin receptor V2. It has prolonged antidiuretic activity, but little pressor effects. It also modulates levels of circulating factor VIII and von Willebrand factor. [NIH] Developmental Biology: The field of biology which deals with the process of the growth and differentiation of an organism. [NIH] Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH]

Dictionary 109

Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] 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] Dihydrotestosterone: Anabolic agent. [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] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] 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] 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] Duct: A tube through which body fluids pass. [NIH] Dysgenesis: Defective development. [EU] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Ectoderm: The outer of the three germ layers of the embryo. [NIH] Ectodermal Dysplasia: A group of hereditary disorders involving tissues and structures derived from the embryonic ectoderm. They are characterized by the presence of abnormalities at birth and involvement of both the epidermis and skin appendages. They are generally nonprogressive and diffuse. Various forms exist, including anhidrotic and hidrotic dysplasias, focal dermal hypoplasia, and aplasia cutis congenita. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Encephalocele: Cerebral tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual

110

Holoprosencephaly

defects, psychomotor developmental delay, and persistent motor deficits frequently occur. [NIH]

Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endoderm: The inner of the three germ layers of the embryo. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] Enhancers: Transcriptional element in the virus genome. [NIH] Enterotoxins: Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria. [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] Ependyma: A thin membrane that lines the ventricles of the brain and the central canal of the spinal cord. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [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] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical

Dictionary 111

disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Extracellular: Outside a cell or cells. [EU] Extraocular: External to or outside of the eye. [NIH] Facial: Of or pertaining to the face. [EU] Factor V: Heat- and storage-labile plasma glycoprotein which accelerates the conversion of prothrombin to thrombin in blood coagulation. Factor V accomplishes this by forming a complex with factor Xa, phospholipid, and calcium (prothrombinase complex). Deficiency of factor V leads to Owren's disease. [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] Femoral: Pertaining to the femur, or to the thigh. [EU] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fetal Alcohol Syndrome: A disorder occurring in children born to alcoholic women who continue to drink heavily during pregnancy. Common abnormalities are growth deficiency (prenatal and postnatal), altered morphogenesis, mental deficiency, and characteristic facies - small eyes and flattened nasal bridge. Fine motor dysfunction and tremulousness are observed in the newborn. [NIH] Fetal Movement: Motion of the fetus perceived by the mother and felt by palpation of the abdomen. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroid: A benign smooth muscle tumor, usually in the uterus or gastrointestinal tract. Also called leiomyoma. [NIH] Fibula: The bone of the lower leg lateral to and smaller than the tibia. In proportion to its length, it is the most slender of the long bones. [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] Follicles: Shafts through which hair grows. [NIH] Forskolin: Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant Coleus forskohlii. Has antihypertensive, positive ionotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. [NIH] Fossa: A cavity, depression, or pit. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH]

112

Holoprosencephaly

Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] 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 Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [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] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germ Layers: The three layers of cells comprising the early embryo. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [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

Dictionary 113

participate in blood production. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [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] 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 follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [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]

Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [NIH] Histone Deacetylase: Hydrolyzes N-acetyl groups on histones. [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] Homeobox: Distinctive sequence of DNA bases. [NIH] Homeodomain Proteins: Proteins encoded by homeobox genes that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (gene expression regulation, developmental). [NIH] Homodimer: Protein-binding "activation domains" always combine with identical proteins. [NIH]

114

Holoprosencephaly

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] 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] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydronephrosis: Abnormal enlargement of a kidney, which may be caused by blockage of the ureter (such as by a kidney stone) or chronic kidney disease that prevents urine from draining into the bladder. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypertelorism: Abnormal increase in the interorbital distance due to overdevelopment of the lesser wings of the sphenoid. [NIH] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypopituitarism: Diminution or cessation of secretion of one or more hormones from the anterior pituitary gland (including LH; FSH; somatotropin; and corticotropin). This may result from surgical or radiation ablation, non-secretory pituitary neoplasms, metastatic tumors, infarction, pituitary apoplexy, infiltrative or granulomatous processes, and other conditions. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypothalamic: Of or involving the hypothalamus. [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 function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Dictionary 115

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] 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] Incisor: Anything adapted for cutting; any one of the four front teeth in each jaw. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [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] 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] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] 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] Integrase: An enzyme that inserts DNA into the host genome. It is encoded by the pol gene of retroviruses and also by temperate bacteriophages, the best known being bacteriophage lambda. EC 2.7.7.-. [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] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions. [NIH] Interorbital: Between the orbits. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Interspecific: Occurring among members of different species. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [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]

116

Holoprosencephaly

Intracellular Membranes: Membranes of subcellular structures. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intraocular: Within the eye. [EU] Intraocular pressure: Pressure of the fluid inside the eye; normal IOP varies among individuals. [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]

Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [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] 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 stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] 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] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Leiomyoma: A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the uterus and the gastrointestinal tract but can occur in the skin and subcutaneous tissues, probably arising from the smooth muscle of small blood vessels in these tissues. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Limb Bud: A swelling on the trunk of the vertebrate embryo that becomes a limb. Limb bud

Dictionary 117

cultures are used in developmental, organogenesis, morphogenesis, and cell differentiation studies. The limb bud of the chick embryo is most commonly used but mouse and rat limb buds are also used. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [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] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [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] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy 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] Malformation: A morphologic developmental process. [EU]

defect

resulting

from

an

intrinsically

abnormal

Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [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] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megalencephaly: A condition in which there is an abnormally large, heavy, and usually malfunctioning brain. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [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 deficiency: A condition of arrested or incomplete development of mind from inherent causes or induced by disease or injury. [NIH] 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]

118

Holoprosencephaly

Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesoderm: The middle germ layer of the embryo. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] MI: 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] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [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] Motor Neurons: Neurons which activate muscle cells. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Nasal Septum: The partition separating the two nasal cavities in the midplane, composed of cartilaginous, membranous and bony parts. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United

Dictionary 119

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] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [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 Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] 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] 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 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] 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] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade

120

Holoprosencephaly

of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic cup: The white, cup-like area in the center of the optic disc. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [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] Organogenesis: Clonal propagation which involves culturing explants from roots, leaves, or stems to form undifferentiated callus tissue; after the cells form shoots, they are separated and rooted. Alternatively, if the callus is put in liquid culture, somatic embryos form. [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] Overexpress: An excess of a particular protein on the surface of a cell. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palpation: Application of fingers with light pressure to the surface of the body to determine consistence of parts beneath in physical diagnosis; includes palpation for determining the outlines of organs. [NIH] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancuronium: A bis-quaternary steroid that is a competitive nicotinic antagonist. As a neuromuscular blocking agent it is more potent than curare but has less effect on the circulatory system and on histamine release. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] 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] Particle: A tiny mass of material. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [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] Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH]

Dictionary 121

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] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] 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] 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 "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]

Pituitary Apoplexy: Sudden hemorrhage or ischemic necrosis involving the pituitary gland which may be associated with acute visual loss, severe headache, meningeal signs, cranial nerve palsies, panhypopituitarism, and rarely coma. The most common cause is hemorrhage (intracranial hemorrhages) related to a pituitary adenoma. Ischemia, meningitis, intracranial hypertension, and other disorders may be associated with this condition. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Pituitary Neoplasms: Neoplasms which arise from or metastasize to the pituitary gland. The majority of pituitary neoplasms are adenomas, which are divided into non-secreting and secreting forms. Hormone producing forms are further classified by the type of hormone they secrete. Pituitary adenomas may also be characterized by their staining properties (adenoma, basophil; adenoma, acidophil; and adenoma, chromophobe). Pituitary

122

Holoprosencephaly

tumors may compress adjacent structures, including the hypothalamus, several cranial nerves, and the optic chiasm. Chiasmal compression may result in bitemporal hemianopsia. [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] 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] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [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] Popliteal: Compression of the nerve at the neck of the fibula. [NIH] 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] Postnatal: Occurring after birth, with reference to the newborn. [EU] Post-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [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, 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] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [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] Pregnancy Tests: Tests to determine whether or not an individual is pregnant. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation embryo, fetus, or pregnant female before birth. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Projection: A defense mechanism, operating unconsciously, whereby that which is

Dictionary 123

emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prosencephalon: The part of the brain developed from the most rostral of the three primary vesicles of the embryonic neural tube and consisting of the diencephalon and telencephalon. [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 Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [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] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [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] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [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] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [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] Putamen: The largest and most lateral of the basal ganglia lying between the lateral medullary lamina of the globus pallidus and the external capsule. It is part of the neostriatum and forms part of the lentiform nucleus along with the globus pallidus. [NIH] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Pyridoxal Phosphate: 3-Hydroxy-2-methyl-5-((phosphonooxy)methyl)-4pyridinecarboxaldehyde. An enzyme co-factor vitamin. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] 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] Radioactive: Giving off radiation. [NIH] Radiography: Examination of any part of the body for diagnostic purposes by means of

124

Holoprosencephaly

roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [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] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinoid: Vitamin A or a vitamin A-like compound. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve

Dictionary 125

impulses to the brain. [NIH] Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Satellite Viruses: Defective viruses which can multiply only by association with a helper virus which complements the defective gene. Satellite viruses may be associated with certain plant viruses, animal viruses, or bacteriophages. They differ from satellite RNA in that satellite viruses encode their own coat protein. [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] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] 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 Turcica: A bony prominence situated on the upper surface of the body of the sphenoid bone. It houses the pituitary gland. [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 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] Septum: A dividing wall or partition; a general term for such a structure. The term is often used alone to refer to the septal area or to the septum pellucidum. [EU] Septum Pellucidum: A triangular double membrane separating the anterior horns of the lateral ventricles of the brain. It is situated in the median plane and bounded by the corpus callosum and the body and columns of the fornix. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Ratio: The number of males per 100 females. [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] 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]

126

Holoprosencephaly

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]

Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] 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] Somatotropin: A small peptide hormone released by the anterior pituitary under hypothalamic control. Somatotropin, or growth hormone, stimulates mitosis, cell growth, and, for some cell types, differentiation in many tissues of the body. It has profound effects on many aspects of gene expression and metabolism. [NIH] Somites: Paired, segmented masses of mesodermal tissue that form along the length of the neural tube during the early stage of embryonic development. They give rise to the vertebral column and other tissues including voluntary muscle, bone, connective tissue, and the dermal layers of the skin. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] 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] Spectrin: A high molecular weight (220-250 kDa) water-soluble protein which can be extracted from erythrocyte ghosts in low ionic strength buffers. The protein contains no lipids or carbohydrates, is the predominant species of peripheral erythrocyte membrane proteins, and exists as a fibrous coating on the inner, cytoplasmic surface of the membrane. [NIH]

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] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [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]

Dictionary 127

Spinous: Like a spine or thorn in shape; having spines. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stenosis: Narrowing or stricture of a duct or canal. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stillbirth: The birth of a dead fetus or baby. [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] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [NIH] 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] Subcutaneous: Beneath the skin. [NIH] Subependymal: Below the ependyma (the membrane that lines the ventricles of the brain and the central canal of the spinal cord). [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] Subthalamus: A transition zone in the anterior part of the diencephalon interposed between the thalamus, hypothalamus, and tegmentum of the mesencephalon. Components of the subthalamus include the subthalamic nucleus, zona incerta, nucleus of field H, and the nucleus of ansa lenticularis. The latter contains the entopeduncular nucleus. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Synostosis: The joining of contiguous and separate bones by osseous tissue. [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] 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] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Teratogens: An agent that causes the production of physical defects in the developing embryo. [NIH] Teratoma: A type of germ cell tumor that may contain several different types of tissue, such as hair, muscle, and bone. Teratomas occur most often in the ovaries in women, the testicles in men, and the tailbone in children. Not all teratomas are malignant. [NIH]

128

Holoprosencephaly

Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [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]

Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [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] 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] 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] 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] Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGFbeta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins. [NIH]

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]

Dictionary 129

Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [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] Ultrasonography: The visualization of deep structures of the body by recording the reflections of echoes of pulses of ultrasonic waves directed into the tissues. Use of ultrasound for imaging or diagnostic purposes employs frequencies ranging from 1.6 to 10 megahertz. [NIH] Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to 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] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoactive Intestinal Peptide: A highly basic, single-chain polypeptide isolated from the intestinal mucosa. It has a wide range of biological actions affecting the cardiovascular, gastrointestinal, and respiratory systems. It is also found in several parts of the central and peripheral nervous systems and is a neurotransmitter. [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] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertebral: Of or pertaining to a vertebra. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH]

130

Holoprosencephaly

Viral: Pertaining to, caused by, or of the nature of virus. [EU] 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] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [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] Volition: Voluntary activity without external compulsion. [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]

Xenograft: The cells of one species transplanted to another species. [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] Zebrafish: A species of North American fishes of the family Cyprinidae. They are used in embryological studies and to study the effects of certain chemicals on development. [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]

131

INDEX A Abdomen, 99, 111, 117, 121, 127, 130 Abdominal, 99, 121 Aberrant, 8, 9, 15, 22, 99 Ablation, 99, 114 Acylation, 5, 99 Adaptability, 99, 104 Adenylate Cyclase, 99, 111 Adverse Effect, 5, 99, 125 Agenesis, 23, 26, 45, 48, 53, 54, 55, 99 Alanine, 39, 99 Algorithms, 99, 102 Alleles, 20, 99 Alternative medicine, 76, 99 Amino acid, 12, 99, 100, 111, 113, 121, 122, 123, 128, 129 Amino Acid Sequence, 99, 100, 111 Amnion, 74, 99, 100 Amniotic Fluid, 99, 100, 112 Anaesthesia, 100, 115 Analog, 100, 108 Analogous, 11, 100, 128 Anaphylatoxins, 100, 106 Anatomical, 100, 101, 104, 115 Animal model, 11, 100 Aniridia, 11, 100 Anomalies, 11, 12, 32, 41, 44, 45, 51, 58, 74, 100, 127 Anophthalmia, 6, 15, 100 Anterior Cerebral Artery, 23, 100 Antibacterial, 100, 126 Antibiotic, 100, 126 Antibodies, 4, 14, 100, 122 Antibody, 14, 100, 101, 105, 114, 115 Anticoagulant, 100, 123 Antidiuretic, 100, 101, 108 Antigen, 100, 101, 106, 113, 114, 115 Antigen-Antibody Complex, 101, 106 Antihypertensive, 101, 111 Aorta, 101, 129 Aplasia, 101, 109 Aqueous, 101, 108, 116 Argipressin, 101, 108 Arterial, 101, 107, 123 Arteries, 101, 102, 107, 118 Artery, 100, 101, 107, 125 Assay, 14, 101 Ataxia, 101, 114

Atrium, 101, 107, 129 Atypical, 26, 47, 101 Axons, 101, 115, 120 B Bacteria, 100, 101, 110, 118, 126, 128 Bactericidal, 101, 110 Bacteriophage, 101, 115, 128 Bacteriophage lambda, 101, 115 Basal cell carcinoma, 8, 9, 13, 16, 19, 21, 102 Basal cells, 102 Basal Ganglia, 50, 101, 102, 103, 105, 112, 114, 123 Basal Ganglia Diseases, 101, 102, 105, 114 Benign, 102, 103, 111, 112, 113, 116 Benign tumor, 102, 116 Bilateral, 6, 11, 28, 38, 40, 74, 102 Bile, 102, 111, 117, 127 Bile duct, 102 Biliary, 18, 102 Biochemical, 6, 9, 14, 23, 99, 102, 116 Biological Transport, 102, 109 Biosynthesis, 102, 111 Biotechnology, 22, 76, 83, 102 Bladder, 102, 114, 115, 129 Blood vessel, 102, 103, 104, 105, 107, 116, 118, 126, 128, 129 Bone Marrow, 102, 112, 117 Brachial, 28, 102 Bradycardia, 56, 102 Brain Neoplasms, 103, 114 Brain Stem, 103, 104 Buffers, 103, 126 C Calcium, 103, 106, 111 Callus, 103, 109, 120 Carbohydrates, 103, 126 Carboxy, 21, 103 Carboxy-terminal, 21, 103 Carcinogenesis, 17, 103 Carcinoma, 103 Cardiovascular, 8, 103, 129 Carotene, 103, 124 Case report, 25, 28, 30, 37, 38, 42, 46, 54, 103 Cataracts, 6, 11, 103 Caudal, 15, 103, 109, 114, 122 Causal, 12, 103

132

Holoprosencephaly

Causality, 28, 103 Cell Death, 4, 104, 119 Cell Differentiation, 19, 104, 117 Cell Division, 101, 104, 115, 122, 125 Cell proliferation, 9, 104 Central Nervous System, 4, 15, 21, 99, 103, 104, 112, 113, 114, 120 Central Nervous System Infections, 104, 113, 114 Cerebellum, 7, 103, 104 Cerebral Cortex, 7, 26, 58, 101, 104, 111, 115, 119 Cerebral Palsy, 104, 126 Cerebrospinal, 104, 114 Cerebrospinal fluid, 104, 114 Cerebrum, 104, 127 Chemotactic Factors, 104, 106 Chin, 104, 117 Choanal Atresia, 45, 104 Cholesterol, 5, 16, 62, 102, 104, 127 Chorea, 37, 104, 105 Choreatic Disorders, 104, 105 Choroid, 105, 124 Chromosomal, 28, 35, 36, 62, 74, 89, 105, 113, 118, 125 Chromosome, 23, 24, 28, 31, 36, 37, 40, 43, 44, 51, 52, 53, 60, 62, 105, 113, 118, 125, 129 Chromosome Abnormalities, 105 Chronic, 29, 105, 108, 114, 116 Circulatory system, 19, 105, 120 CIS, 17, 21, 105, 124 Cleft Lip, 23, 25, 27, 35, 40, 46, 58, 59, 105 Cleft Palate, 25, 27, 47, 105 Clinical Medicine, 105, 122 Clinical trial, 3, 83, 105 Cloning, 9, 13, 102, 105 Cofactor, 105, 123, 128 Collagen, 99, 105, 122 Coloboma, 25, 51, 105 Combinatorial, 21, 105 Complement, 5, 100, 105, 106, 112 Complementary and alternative medicine, 71, 72, 106 Complementary medicine, 71, 106 Computational Biology, 83, 106 Computed tomography, 29, 53, 106 Computerized axial tomography, 106 Computerized tomography, 106 Conception, 106, 111 Cones, 107, 124 Congenita, 107, 109

Connective Tissue, 102, 105, 107, 112, 118, 126 Contraindications, ii, 107 Coordination, 15, 104, 107 Cor, 107, 114 Corneum, 107, 110 Coronary, 107, 118 Coronary Thrombosis, 107, 118 Corpus, 31, 45, 61, 107, 125, 130 Corpus Callosum, 31, 45, 61, 107, 125 Cortex, 7, 107 Cortical, 107, 125 Cranial, 4, 15, 18, 104, 107, 113, 116, 119, 120, 121, 122, 126 Craniocerebral Trauma, 102, 107, 113, 114 Craniofacial Abnormalities, 25, 107 Criterion, 32, 108 Crossing-over, 108, 124 Cultured cells, 16, 108 Curare, 108, 120 Cyclic, 4, 99, 101, 108, 111 Cyclopia, 4, 11, 18, 30, 33, 36, 39, 40, 46, 55, 108 Cyst, 30, 32, 38, 61, 108 Cytoplasm, 108, 110 Cytoskeletal Proteins, 18, 108 Cytoskeleton, 108 D De novo, 31, 40, 54, 108 Defective Viruses, 5, 108 Deletion, 31, 37, 39, 44, 55, 60, 61, 108 Dendrites, 108, 119 Dermal, 108, 109, 126 Desmopressin, 60, 108 Developmental Biology, 10, 30, 46, 52, 108 Diabetes Insipidus, 25, 46, 60, 101, 108 Diagnostic procedure, 76, 108 Diarrhea, 108, 110 Diencephalon, 13, 50, 109, 110, 114, 123, 127, 128 Diffusion, 16, 40, 102, 109 Digestion, 102, 109, 117, 127, 129 Dihydrotestosterone, 109, 124 Dilation, 109, 114 Diploid, 109, 118, 122, 129 Direct, iii, 6, 12, 16, 17, 105, 109, 124 Discrete, 17, 109 Disinfectant, 109, 111 Distal, 31, 43, 109 Dorsal, 7, 15, 19, 32, 61, 109, 110, 119, 122, 125 Dorsum, 109, 112

133

Duct, 109, 127 Dysgenesis, 26, 32, 35, 47, 51, 74, 109 Dysplasia, 37, 74, 109 E Ectoderm, 8, 12, 17, 109, 119 Ectodermal Dysplasia, 74, 109 Effector, 106, 109 Elastic, 37, 109 Embryo, 4, 10, 16, 17, 19, 21, 99, 104, 109, 110, 112, 115, 116, 118, 122, 127 Embryogenesis, 17, 18, 109 Encephalocele, 34, 50, 109 Endemic, 110, 127 Endocytosis, 20, 110 Endoderm, 7, 110 Endogenous, 17, 110, 128 Endotoxins, 106, 110 Enhancers, 8, 110 Enterotoxins, 5, 110 Environmental Health, 82, 84, 110 Enzymatic, 99, 103, 106, 110, 113, 124 Enzyme, 23, 99, 109, 110, 112, 115, 118, 122, 123, 124, 128, 130 Ependyma, 110, 127 Epidemic, 110, 127 Epidermis, 9, 102, 107, 109, 110 Epinephrine, 110, 119, 129 Epithalamus, 109, 110 Epithelial, 14, 18, 102, 110 Epithelial Cells, 110 Epithelium, 15, 110, 116 Ethanol, 4, 110 Eukaryotic Cells, 108, 111, 119, 120 Exogenous, 4, 5, 110, 111, 112 Exon, 17, 111 Extracellular, 13, 16, 18, 107, 110, 111 Extraocular, 15, 111 F Facial, 4, 5, 9, 12, 19, 24, 28, 44, 51, 55, 58, 59, 61, 62, 65, 74, 88, 108, 111 Factor V, 111, 123 Family Planning, 83, 111 Fat, 102, 103, 107, 111, 126 Femoral, 74, 111 Femur, 111 Fetal Alcohol Syndrome, 3, 111 Fetal Movement, 60, 111 Fetus, 40, 48, 53, 54, 55, 57, 63, 111, 122, 127, 129 Fibroid, 111, 116 Fibula, 111, 122 Fissure, 105, 107, 111

Follicles, 111 Forskolin, 5, 111 Fossa, 104, 111 Frontal Lobe, 100, 111 G Gallbladder, 99, 102, 111 Ganglia, 102, 112, 119, 121 Ganglion, 112, 119, 120 Gas, 109, 112, 114, 124 Gastrin, 112, 114 Gastrointestinal, 17, 110, 111, 112, 116, 129 Gastrointestinal tract, 110, 111, 112, 116 Gene Expression, 13, 14, 21, 112, 113, 126 Gene Targeting, 7, 112 Gene Therapy, 5, 112 Genetic Engineering, 102, 105, 112 Genotype, 59, 112, 121 Germ Cells, 112, 120, 126 Germ Layers, 7, 109, 110, 112 Gestation, 53, 54, 105, 112, 121 Gestational, 25, 112 Gestational Age, 25, 112 Gland, 112, 121, 125, 128 Glycine, 99, 113, 119 Governing Board, 113, 122 Grafting, 5, 113 Gyrus Cinguli, 100, 113 H Hair follicles, 9, 113 Haploid, 8, 113, 122 Headache, 113, 114, 121 Hematopoiesis, 34, 113 Hemoglobinopathies, 112, 113 Hereditary, 100, 105, 109, 113 Heredity, 112, 113 Heterogeneity, 18, 29, 44, 113 Histamine, 100, 113, 120 Histamine Release, 100, 113, 120 Histone Deacetylase, 12, 113 Histones, 113 Homeobox, 10, 18, 113 Homeodomain Proteins, 12, 113 Homodimer, 113, 128 Homologous, 99, 108, 112, 114, 125 Hormone, 10, 101, 108, 110, 112, 114, 117, 121, 126, 128 Human Development, 8, 10, 11, 34, 82, 114 Hydrocephalus, 45, 71, 114, 116 Hydrogen, 103, 114, 118 Hydrolysis, 114, 122, 123 Hydronephrosis, 28, 114 Hydroxyproline, 99, 105, 114

134

Holoprosencephaly

Hypertelorism, 27, 40, 114 Hypokinesia, 46, 114 Hypopituitarism, 10, 114 Hypoplasia, 12, 17, 19, 51, 60, 109, 114 Hypothalamic, 60, 114, 126 Hypothalamus, 103, 109, 114, 121, 122, 125, 127 I Immune function, 114, 128 Immune response, 10, 100, 114, 130 Immune system, 114, 115, 130 Immunologic, 104, 112, 115 Impairment, 74, 101, 115, 117, 118 In situ, 8, 115 In vitro, 5, 15, 17, 112, 115 In vivo, 5, 10, 17, 20, 112, 115 Incisor, 11, 18, 51, 58, 59, 115 Incontinence, 114, 115 Induction, 8, 10, 16, 115 Infarction, 107, 114, 115, 118 Initiation, 115, 128 Insight, 6, 8, 9, 21, 74, 115 Integrase, 17, 115 Internal Capsule, 100, 115 Interneurons, 7, 115 Interorbital, 114, 115 Interphase, 115, 119 Interspecific, 14, 115 Interstitial, 31, 115 Intestinal, 103, 110, 115, 129 Intestinal Mucosa, 115, 129 Intestines, 99, 112, 115, 125 Intracellular, 5, 13, 17, 20, 115, 116, 117 Intracellular Membranes, 116, 117 Intracranial Hemorrhages, 114, 116, 121 Intracranial Hypertension, 113, 114, 116, 121 Intraocular, 105, 111, 116 Intraocular pressure, 111, 116 Invasive, 116, 117 Invertebrates, 6, 116 Involuntary, 5, 102, 104, 116, 118 Iris, 100, 116 K Kb, 44, 82, 116 Kidney Disease, 39, 82, 114, 116 Kidney stone, 114, 116 L Labile, 105, 111, 116 Larynx, 116, 130 Lectin, 116, 117 Leiomyoma, 37, 111, 116

Lens, 10, 103, 107, 116, 130 Lesion, 20, 116, 117 Lethargy, 114, 116 Leukemia, 112, 116 Ligands, 20, 116 Limb Bud, 14, 116 Lip, 22, 29, 59, 105, 117 Liver, 17, 99, 102, 111, 117 Localization, 18, 28, 62, 117 Localized, 13, 117, 122 Lymph, 105, 117 Lymphatic, 117, 118 Lymphoid, 100, 117 M Magnetic Resonance Imaging, 60, 117 Malformation, 4, 7, 13, 14, 19, 29, 36, 44, 51, 52, 64, 89, 117 Malignant, 103, 117, 127 Maxillary, 11, 51, 58, 59, 105, 117 Medial, 105, 113, 117, 125, 126 Mediate, 13, 20, 117 MEDLINE, 83, 117 Megalencephaly, 7, 117 Melanin, 116, 117, 121, 129 Membrane, 8, 14, 99, 104, 105, 106, 110, 111, 116, 117, 120, 122, 124, 125, 126, 127, 129, 130 Membrane Proteins, 8, 117, 126 Meninges, 104, 107, 117 Mental, iv, 3, 6, 11, 15, 38, 44, 82, 84, 104, 111, 114, 117, 118, 123 Mental deficiency, 111, 117 Mental Disorders, 114, 117 Mental Retardation, 11, 38, 44, 118 Mentors, 16, 118 Mesenchymal, 14, 118 Mesoderm, 7, 21, 105, 118 Metabolic disorder, 108, 118 Metastatic, 103, 114, 118 MI, 97, 118 Microbiology, 101, 118 Migration, 25, 105, 118 Modification, 16, 99, 112, 118 Molecule, 4, 15, 99, 101, 106, 109, 113, 114, 116, 118, 124, 129 Monitor, 118, 119 Monosomy, 41, 54, 55, 64, 118 Morphological, 4, 109, 118 Morphology, 8, 14, 18, 47, 118 Mosaicism, 54, 118 Motor Neurons, 21, 118 Musculature, 114, 118

135

Myocardium, 118 N Nasal Septum, 11, 118 NCI, 1, 81, 105, 118 Necrosis, 115, 118, 119, 121 Neocortex, 6, 119 Nerve, 51, 101, 104, 108, 112, 119, 120, 121, 122, 124 Nervous System, 7, 17, 20, 22, 52, 55, 57, 62, 65, 104, 119, 121 Networks, 8, 11, 119 Neural, 4, 6, 7, 14, 17, 19, 21, 38, 49, 59, 88, 109, 119, 123, 125, 126 Neural Crest, 4, 19, 119 Neurologic, 109, 114, 119 Neuromuscular, 119, 120 Neuronal, 5, 21, 25, 64, 119 Neurons, 5, 7, 16, 21, 31, 108, 112, 115, 118, 119 Neurotransmitter, 99, 113, 119, 129 Nuclear, 18, 102, 111, 112, 115, 119, 128 Nuclei, 27, 110, 112, 113, 117, 119, 120, 125 Nucleolus, 21, 119 Nucleus, 12, 100, 101, 102, 108, 111, 119, 123, 125, 127 O Opacity, 103, 119 Operon, 119, 124 Opsin, 120, 124 Optic cup, 100, 120 Optic Nerve, 120, 124 Organelles, 108, 120 Organogenesis, 117, 120 Ovaries, 43, 120, 127 Ovary, 9, 120 Overexpress, 4, 120 Ovum, 112, 120, 130 P Palate, 25, 40, 47, 51, 105, 120 Palpation, 111, 120 Palsy, 38, 45, 120 Pancuronium, 60, 120 Paralysis, 108, 120, 126 Parietal, 100, 120, 121 Parietal Lobe, 100, 120 Particle, 120, 128 Pathogenesis, 16, 63, 120 Pathologic, 56, 107, 120, 124 Pedigree, 11, 120 Pelvis, 99, 116, 120, 121, 129 Peptide, 16, 59, 99, 121, 122, 123, 126 Perinatal, 6, 34, 121

Peripheral Nervous System, 119, 120, 121, 129 Peritoneal, 28, 121 Peritoneum, 121 Pharmacologic, 121, 128 Phenotype, 4, 11, 17, 20, 28, 121 Phenylalanine, 121, 129 Phosphorus, 103, 121 Phosphorylation, 18, 121 Physical Examination, 112, 121 Physiologic, 102, 114, 121, 124 Pigments, 103, 121, 124 Pituitary Apoplexy, 114, 121 Pituitary Gland, 10, 111, 114, 121, 125 Pituitary Neoplasms, 114, 121 Plants, 116, 118, 121, 122 Plasma, 99, 100, 111, 122 Plasma cells, 100, 122 Platelet Aggregation, 100, 111, 122 Pneumonia, 107, 122 Polymerase, 122, 124 Polypeptide, 99, 103, 105, 122, 129, 130 Popliteal, 74, 122 Posterior, 8, 101, 104, 105, 109, 110, 115, 116, 120, 122, 126 Postnatal, 6, 13, 21, 28, 111, 122, 127 Post-translational, 13, 122 Practice Guidelines, 84, 122 Precipitating Factors, 103, 122 Precursor, 12, 109, 110, 121, 122, 128, 129 Pregnancy Tests, 112, 122 Prenatal, 8, 23, 24, 27, 30, 31, 33, 38, 39, 41, 43, 46, 48, 53, 54, 55, 56, 57, 61, 63, 109, 111, 122 Prenatal Diagnosis, 23, 24, 30, 31, 33, 38, 41, 43, 46, 48, 53, 54, 55, 57, 61, 63, 122 Progression, 100, 122 Projection, 115, 120, 122 Prosencephalon, 46, 109, 123, 127 Protein C, 17, 99, 101, 108, 123, 126 Protein Kinases, 9, 123 Protein S, 13, 102, 123 Proteinuria, 39, 123 Proteolytic, 20, 106, 123 Psychic, 117, 123, 125 Psychomotor, 110, 123 Public Policy, 83, 123 Publishing, 74, 88, 123 Pulmonary, 60, 107, 123, 124, 129 Pulmonary Artery, 123, 129 Putamen, 100, 102, 123 Pyridoxal, 71, 123

136

Holoprosencephaly

Pyridoxal Phosphate, 71, 123 Q Quaternary, 120, 123 R Race, 118, 123 Radiation, 114, 123, 130 Radioactive, 114, 119, 123 Radiography, 112, 123 Radiological, 56, 58, 124 Radiology, 26, 40, 47, 61, 124 Receptor, 12, 13, 14, 16, 18, 20, 28, 49, 101, 108, 124 Recombinant, 54, 124, 129 Recombination, 39, 112, 124 Reductase, 23, 124 Refer, 1, 105, 115, 117, 124, 125 Refraction, 124, 126 Regeneration, 5, 124 Relaxant, 111, 124 Repressor, 12, 120, 124 Resorption, 114, 124 Respiratory System, 124, 129 Retina, 10, 105, 107, 116, 120, 124, 125, 130 Retinal, 6, 11, 15, 120, 124 Retinoid, 14, 124 Retinol, 124 Retroviral vector, 112, 124 Rhodopsin, 120, 124 Rods, 124, 125 S Satellite, 108, 125 Satellite Viruses, 108, 125 Screening, 16, 48, 105, 125 Secretion, 113, 114, 125, 128, 129 Secretory, 114, 125 Segmentation, 125 Segregation, 57, 124, 125 Seizures, 34, 125 Sella Turcica, 109, 121, 125 Septal, 100, 125 Septal Nuclei, 100, 125 Septum, 12, 125 Septum Pellucidum, 125 Serum, 100, 105, 125 Sex Ratio, 59, 125 Side effect, 99, 125, 128 Skeletal, 12, 14, 108, 125 Skeleton, 111, 125, 126 Skull, 23, 107, 109, 126, 127 Small intestine, 114, 115, 126, 129 Smooth muscle, 100, 111, 113, 116, 126 Soft tissue, 14, 102, 125, 126

Solvent, 111, 126 Soma, 126 Somatic, 39, 109, 120, 121, 126 Somatotropin, 114, 126 Somites, 19, 126 Spastic, 45, 126 Specialist, 90, 109, 126 Species, 8, 11, 101, 108, 110, 115, 118, 123, 126, 127, 130 Spectrin, 18, 126 Spectrum, 18, 32, 36, 50, 51, 63, 74, 126 Sperm, 105, 126, 128 Sphenoid, 114, 125, 126 Spina bifida, 17, 28, 126 Spinal cord, 7, 19, 20, 102, 103, 104, 110, 112, 117, 119, 121, 126, 127 Spinous, 110, 127 Sporadic, 11, 26, 127 Stem Cells, 6, 9, 17, 127 Stenosis, 29, 30, 50, 127 Steroid, 120, 127 Stillbirth, 28, 127 Stomach, 99, 112, 114, 115, 126, 127 Stricture, 127 Subclinical, 125, 127 Subcutaneous, 116, 127 Subependymal, 37, 127 Subspecies, 126, 127 Subthalamus, 109, 127 Suppression, 13, 127 Synostosis, 74, 127 T Telencephalon, 102, 104, 123, 127 Temporal, 17, 127 Teratogenic, 22, 127 Teratogens, 4, 127 Teratoma, 74, 127 Testicles, 127, 128 Testosterone, 124, 128 Thalamus, 61, 103, 109, 110, 127, 128 Thigh, 111, 128 Thrombin, 111, 122, 123, 128 Thrombomodulin, 123, 128 Thrombosis, 123, 128 Thyroid, 128, 129 Tomography, 29, 128 Topical, 68, 110, 128 Toxic, iv, 108, 110, 128 Toxicology, 84, 128 Transcription Factors, 13, 20, 128 Transduction, 9, 21, 128 Transfection, 15, 102, 112, 128

137

Transforming Growth Factor beta, 18, 128 Translation, 99, 128 Translational, 129 Translocation, 34, 35, 36, 44, 63, 129 Trisomy, 41, 48, 54, 55, 64, 129 Tyrosine, 11, 129 U Ultrasonography, 33, 36, 112, 129 Ureter, 114, 129 Urinary, 114, 115, 129 Urine, 100, 102, 108, 114, 115, 116, 123, 129 Uterus, 107, 111, 116, 120, 129 V Vacuoles, 110, 120, 129 Vasoactive, 28, 129 Vasoactive Intestinal Peptide, 28, 129 Vector, 128, 129 Vein, 119, 125, 129 Venous, 32, 123, 129 Venter, 129 Ventral, 4, 10, 13, 15, 18, 20, 21, 38, 114, 129 Ventricle, 6, 56, 107, 110, 114, 123, 128, 129 Ventricular, 32, 107, 114, 129 Vertebrae, 126, 129

Vertebral, 126, 129 Veterinary Medicine, 83, 129 Villi, 114, 129 Viral, 128, 130 Virus, 101, 104, 108, 110, 112, 124, 125, 128, 130 Viscera, 126, 130 Vitreous, 116, 124, 130 Vitreous Body, 124, 130 Vitro, 130 Vivo, 10, 130 Vocal cord, 38, 45, 130 Volition, 116, 130 W White blood cell, 100, 117, 122, 130 X Xenograft, 100, 130 X-ray, 106, 119, 124, 130 Y Yeasts, 121, 130 Z Zebrafish, 4, 8, 10, 13, 19, 130 Zygote, 106, 118, 130 Zymogen, 123, 130

138

Holoprosencephaly

139

140

Holoprosencephaly