Mutations in ZIC2 in human holoprosencephaly: description of a novel ZIC2 specific phenotype and comprehensive analysis of 157 individuals
| Autor: | Raoul C.M. Hennekam, Ann Haskins Olney, Elizabeth Roeder, Sherri J. Bale, Sylvie Odent, Nan Zhou, Mauricio R. Delgado, Robert Long, Véronique David, Elizabeth McPherson, Michelle Clemens, Nancy J. Clegg, Ute Hehr, Aimee D C Paulussen, Erich Roessler, Eric Levey, Ewa Pronicka, Derek A. T. Cummings, Lars-Erik Wehner, Felicitas Lacbawan, Donald W. Hadley, Sandra Mercier, Daniel E. Pineda-Alvarez, Jin S. Hahn, Sue Kenwrick, Sophia M. Bous, Christèle Dubourg, Carol Booth, Elaine E. Stashinko, Amelia A. Keaton, Hubert J T Smeets, Joan Z. Balog, Anna Tylki-Szymańska, Jorge I. Vélez, Maximilian Muenke, Chayim Can Schell-Apacik, Ronald L. Thomas, Emily Hardisty, Kenneth N. Rosenbaum, Benjamin D. Solomon, Dagmar Wieczorek |
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| Přispěvatelé: | Cancer Genetics Branch, National Institute of Health (NIH)-National Human Genome Research Institute (NHGRI), Department of Pathology, State University of New York (SUNY), Institut de Génétique et Développement de Rennes (IGDR), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de génétique clinique, hôpital Sud, Department of Neurology, University of Texas Southwestern Medical Center [Dallas]-Texas Scottish Rite Hospital for Children, Department of Genetics, Children's National Medical Center, University of Nebraska Medical Center, University of Nebraska System-University of Nebraska System-Munroe-Meyer Institute for Genetics and Rehabilitation, Department of Human Genetics, Universität Regensburg (UR)-Center for Human Genetics, GeneDx [Gaithersburg, MD, USA], Department of Clinical Genetics, Academic Hospital Maastricht, Department of Obstetrics and Gynecology, University of Chapel Hill School of Medicine, Clinic of Metabolic Diseases, Endocrinology and Diabetology, Children's Memorial Health Institute, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Marshfield Clinic, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Department of Neurology and Neurological Sciences [Stanford], Stanford Medicine, Stanford University-Stanford University, Kennedy Krieger Institute, Johns Hopkins University (JHU), Institute of Human Genetics, Universität Duisburg-Essen [Essen], Department of Pediatrics, The University of Texas at San Antonio (UTSA), Institute of Social Pediatric and Adolescent Medicine, Ludwig-Maximilians-Universität München (LMU), Practice of Human Genetics, Lutheran General Hospital, Drexel University College of Medicine, Clinical Genetics, Addenbrooke's Hospital, Service de Génétique Clinique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-hôpital Sud, This research was supported by the Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, United States of America and GIS Maladies Rares GISMR0701/DHOS, France., De Villemeur, Hervé, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, MUMC+: DA KG Lab Centraal Lab (9), Genetica & Celbiologie, RS: CARIM School for Cardiovascular Diseases, RS: GROW - School for Oncology and Reproduction, Universität Duisburg-Essen = University of Duisburg-Essen [Essen], ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, Paediatrics, Faculteit der Geneeskunde |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Proband
Male Medizin Inheritance Patterns [SDV.GEN] Life Sciences [q-bio]/Genetics medicine.disease_cause MESH: Magnetic Resonance Imaging MESH: Genotype Holoprosencephaly Genotype Prevalence [SDV.BDD]Life Sciences [q-bio]/Development Biology Genetics (clinical) Genetics 0303 health sciences Mutation 030305 genetics & heredity Nuclear Proteins MESH: Transcription Factors Magnetic Resonance Imaging 3. Good health Phenotype Female MESH: Holoprosencephaly musculoskeletal diseases medicine.medical_specialty congenital hereditary and neonatal diseases and abnormalities MESH: Mutation Genetic counseling education Biology ZIC2 MESH: Phenotype Genetic determinism Article 03 medical and health sciences Molecular genetics [SDV.BDD] Life Sciences [q-bio]/Development Biology medicine Humans MESH: Prevalence 030304 developmental biology [SDV.GEN]Life Sciences [q-bio]/Genetics MESH: Humans medicine.disease MESH: Male MESH: Inheritance Patterns MESH: Female MESH: Nuclear Proteins Transcription Factors |
| Zdroj: | Journal of Medical Genetics Journal of Medical Genetics, BMJ Publishing Group, 2010, 47 (8), pp.513-24. ⟨10.1136/jmg.2009.073049⟩ Journal of Medical Genetics, 2010, 47 (8), pp.513-24. ⟨10.1136/jmg.2009.073049⟩ Journal of Medical Genetics, 47(8), 513-524. BMJ Publishing Group Journal of medical genetics, 47(8), 513-524. BMJ Publishing Group |
| ISSN: | 0022-2593 1468-6244 |
| DOI: | 10.1136/jmg.2009.073049⟩ |
| Popis: | Holoprosencephaly (HPE) is the most common malformation of the human forebrain, and may be due to cytogenetic anomalies, teratogens, occur in the context of a syndrome, or be due to mutations in single genes associated with non-syndromic HPE. Mutations in ZIC2, a transcription factor located on chromosome 13q32, are the second-most common cause of non-syndromic, non-chromosomal HPE. Blood samples from over 1000 individuals with HPE-spectrum disorders and their relatives were analyzed for sequence variations in ZIC2. We examined clinical details and included all other known previously published and unpublished cases of mutations in ZIC2 through a literature search and collaboration with other centers. We find mutations in ZIC2 in 8% of probands with HPE, and describe 153 individuals from 116 unrelated kindreds, including 137 patients with molecularly-determined mutations in ZIC2 and 16 patients with deletions of the ZIC2 locus. Unlike HPE due to mutations in other genes, the vast majority of cases are sporadic and the proportional distribution of HPE types differs significantly from previously published analyses of non-chromosomal non-syndromic HPE. Furthermore, we describe a novel facial phenotype in patients with mutations in ZIC2 which includes bitemporal narrowing, upsplanting palpebral fissures, a short nose with anteverted nares, and a broad and well-demarcated philtrum, and large ears. This phenotype is distinct from the standard facial dysmorphisms associated with non-chromosomal, non-syndromic HPE. Our findings show that HPE due to mutations in ZIC2 is distinct from that due to mutations in other genes. This may shed light on the mechanisms that contribute to the formation of the face and the forebrain and may help direct genetic counseling and diagnostic strategies. |
| Databáze: | OpenAIRE |
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