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          Institute: MPI für molekulare Genetik     Collection: Department of Human Molecular Genetics     Display Documents



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ID: 308496.0, MPI für molekulare Genetik / Department of Human Molecular Genetics
Mutational spectrum of COH1 and clinical heterogeneity in Cohen syndrome
Authors:Seifert, W.; Holder-Espinasse, M.; Spranger, S.; Hoeltzenbein, Maria; Rossier, E.; Dollfus, H.; Lacombe, H.; Verloes, A.; Chrzanowska, K. H.; Maegawa, G. H. B.; Chitayat, D.; Kotzot, D.; Huhle, D.; Meinecke, P.; Albrecht, B.; Mathijssen, I.; Leheup, B.; Raile, K.; Hennies, H. C.; Horn, D.
Language:English
Date of Publication (YYYY-MM-DD):2006-01-25
Title of Journal:Journal of Medical Genetics
Journal Abbrev.:J Med Genet.
Volume:43
Issue / Number:5
Start Page:e22
End Page:e22
Copyright:© 2006 by BMJ Publishing Group Ltd
Review Status:not specified
Audience:Experts Only
Abstract / Description:Cohen syndrome (CS) is an autosomal recessive disorder with variability in the clinical manifestations, characterised by mental retardation, postnatal microcephaly, facial dysmorphism, pigmentary retinopathy, myopia, and intermittent neutropenia. Mutations in the gene COH1 have been found in an ethnically diverse series of patients. Brief clinical descriptions of 24 patients with CS are provided. The patients were from 16 families of different ethnic backgrounds and between 2.5 and 60 years of age at assessment. DNA samples from all patients were analysed for mutations in COH1 by direct sequencing. Splice site mutations were characterised using reverse transcriptase PCR analysis from total RNA samples. In this series, we detected 25 different COH1 mutations; 19 of these were novel, including 9 nonsense mutations, 8 frameshift mutations, 4 verified splice site mutations, 3 larger in frame deletions, and 1 missense mutation. We observed marked variability of developmental and growth parameters. The typical facial gestalt was seen in 23/24 patients. Early onset progressive myopia was present in all the patients older than 5 years. Widespread pigmentary retinopathy was found in 12/14 patients assessed over 5 years of age. We present evidence for extended allelic heterogeneity of CS, with the vast majority of mutations leading to premature termination codons in COH1. Our data confirm the broad clinical spectrum of CS with some patients lacking even the characteristic facial gestalt and pigmentary retinopathy at school age.
Free Keywords:Cohen syndrome; allelic heterogeneity; facial dysmorphism; microcephaly; myopia
Comment of the Author/Creator:Correspondence to:
Dr H C Hennies
Cologne Center for Genomics, University of Cologne, Zülpicher Str. 47, 50674 Köln, Germany; h.hennies@uni-koeln.de
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Hans-Hilger Ropers
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Cologne Center for Genomics, Universität zu Köln, Köln, Germany;
2.Faculty of Biology, Chemistry, and Pharmacy, Free University of Berlin, Germany;
3.Hôpital Jeanne de Flandre, Génétique médicale, CHRU, Lille, France;
4.Praxis für Humangenetik, Bremen, Germany;
5.Department of Human Genetics, University of Ulm, Germany;
6.Centre de Référence pour les Affections Génétique Ophtalmologiques, Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France;
7.Service de Génétique Médicale, Hôpital Pellegrin-Enfants, Bordeaux, France;
8.Unit of Clinical Genetics, Hôpital Robert Debré and INSERM U676, Paris, France;
9.Department of Medical Genetics, Children’s Memorial Health Institute, Warsaw, Poland;
10.Department of Pediatrics, Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada;
11.Division of Clinical Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Austria;
12.Praxis für humangenetische Beratung und Diagnostik, Wetzlar, Germany;
13.Altonaer Kinderkrankenhaus, Hamburg, Germany;
14.Institut für Humangenetik, Universität Essen, Essen, Germany;
15.Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands;
16.Hôpital de Brabois, Service de Génétique, Nancy, France;
17.Department of Pediatric Endocrinology, University of Leipzig, Leipzig, Germany;
18.Institute of Medical Genetics, Charité, University Medicine of Berlin, Germany.
Identifiers:ISSN:1468-6244
DOI:10.1136/jmg.2005.039867
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