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Mutational spectrum of COH1 and clinical heterogeneity in Cohen syndrome
  1. W Seifert1,
  2. M Holder-Espinasse3,
  3. S Spranger4,
  4. M Hoeltzenbein5,
  5. E Rossier6,
  6. H Dollfus7,
  7. D Lacombe8,
  8. A Verloes9,
  9. K H Chrzanowska10,
  10. G H B Maegawa11,
  11. D Chitayat11,
  12. D Kotzot12,
  13. D Huhle13,
  14. P Meinecke14,
  15. B Albrecht15,
  16. I Mathijssen16,
  17. B Leheup17,
  18. K Raile18,
  19. H C Hennies1,
  20. D Horn19
  1. 1Cologne Center for Genomics, Universität zu Köln, Köln, Germany
  2. 2Faculty of Biology, Chemistry, and Pharmacy, Free University of Berlin, Germany
  3. 3Hôpital Jeanne de Flandre, Génétique médicale, CHRU, Lille, France
  4. 4Praxis für Humangenetik, Bremen, Germany
  5. 5Max Planck Institute for Molecular Genetics, Berlin, Germany
  6. 6Department of Human Genetics, University of Ulm, Germany
  7. 7Centre de Référence pour les Affections Génétique Ophtalmologiques, Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
  8. 8Service de Génétique Médicale, Hôpital Pellegrin-Enfants, Bordeaux, France
  9. 9Unit of Clinical Genetics, Hôpital Robert Debré and INSERM U676, Paris, France
  10. 10Department of Medical Genetics, Children’s Memorial Health Institute, Warsaw, Poland
  11. 11Department of Pediatrics, Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
  12. 12Division of Clinical Genetics, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Austria
  13. 13Praxis für humangenetische Beratung und Diagnostik, Wetzlar, Germany
  14. 14Altonaer Kinderkrankenhaus, Hamburg, Germany
  15. 15Institut für Humangenetik, Universität Essen, Essen, Germany
  16. 16Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
  17. 17Hôpital de Brabois, Service de Génétique, Nancy, France
  18. 18Department of Pediatric Endocrinology, University of Leipzig, Leipzig, Germany
  19. 19Institute of Medical Genetics, Charité, University Medicine of Berlin, Germany
  1. Correspondence to:
 Dr H C Hennies
 Cologne Center for Genomics, University of Cologne, Zülpicher Str. 47, 50674 Köln, Germany; h.hennies{at}


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.

  • CS, Cohen syndrome
  • Cohen syndrome
  • allelic heterogeneity
  • facial dysmorphism
  • microcephaly
  • myopia

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  • Competing interests: there are no competing interests.

  • Signed informed consents were obtained from the parents of the affected and unaffected children and guardians of affected adults. The study was approved by the local ethics committee.