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Search for the best indicators for the presence of a VPS13B gene mutation and confirmation of diagnostic criteria in a series of 34 patients genotyped for suspected Cohen syndrome
  1. Salima El Chehadeh1,
  2. Bernard Aral2,
  3. Nadège Gigot1,2,
  4. Christel Thauvin-Robinet1,
  5. Anne Donzel2,
  6. Marie-Ange Delrue3,
  7. Didier Lacombe3,
  8. Albert David4,
  9. Lydie Burglen5,
  10. Nicole Philip6,
  11. Anne Moncla6,
  12. Valérie Cormier-Daire7,
  13. Marlène Rio7,
  14. Patrick Edery8,
  15. Alain Verloes9,
  16. Dominique Bonneau10,
  17. Alexandra Afenjar5,
  18. Aurélia Jacquette11,
  19. Delphine Heron11,
  20. Pierre Sarda12,
  21. Lucile Pinson12,
  22. Bérénice Doray13,
  23. Jacqueline Vigneron14,
  24. Bruno Leheup14,
  25. Anne-Marie Frances-Guidet15,
  26. Gwenaelle Dienne16,
  27. Muriel Holder17,
  28. Alice Masurel-Paulet1,
  29. Frédéric Huet1,
  30. Jean-Raymond Teyssier2,
  31. Laurence Faivre1
  1. 1Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Hôpital d'Enfants, CHU Dijon, Université de Dijon, France
  2. 2Laboratoire de Génétique Moléculaire, Plateau Technique de Biologie, CHU Dijon, Université de Dijon, France
  3. 3Service de Génétique Médicale, CHU Bordeaux, Université de Bordeaux, France
  4. 4Génétique Clinique, CHU Nantes, Université de Nantes, France
  5. 5Unité de génétique clinique et neurogénétique, CHU Armand-Trousseau, APHP, Paris, France
  6. 6Département de génétique médicale, CHU de Marseille, France
  7. 7Département de Génétique, Hôpital Necker - Enfants Malades, APHP, Paris, France
  8. 8Unité de génétique pédiatrique, CHU de Lyon, France
  9. 9Unité fonctionnelle de génétique clinique, CHU Robert Debré, APHP, Paris, France
  10. 10Service de génétique, CHU d'Angers, Université d'Angers, Angers, France
  11. 11Département de génétique, cytogénétique et embryologie, CHU Pitié-Salpêtrière, APHP, Paris, France
  12. 12Service de génétique médicale, CHU de Montpellier, Université de Montpellier, France
  13. 13Service de génétique médicale, CHU de Hautepierre, Université de Strasbourg, Strasbourg, France
  14. 14Département de Génétique, CHU Nancy, Université de Nancy, Nancy, France
  15. 15Service de Génétique, CH Toulon, Toulon, France
  16. 16Service d'Endocrinologie Pédiatrique, Hôpital d'Enfants, Toulouse, Université de Toulouse, France
  17. 17Service de Génétique, Hôpital Jeanne de Flandres, Université de Lille, Lille, France
  1. Correspondence to Laurence Faivre, Centre de Génétique, Hôpital d'Enfants, 10 Bd maréchal de Lattre de Tassigny, Dijon Cedex 21034, France; Laurence.faivre{at}


Background Cohen syndrome is a rare autosomal recessive inherited disorder that results from mutations of the VPS13B gene. Clinical features consist of a combination of mental retardation, facial dysmorphism, postnatal microcephaly, truncal obesity, slender extremities, joint hyperextensibility, myopia, progressive chorioretinal dystrophy, and intermittent neutropenia.

Patients and methods The aim of the study was to determine which of the above clinical features were the best indicators for the presence of VPS13B gene mutations in a series of 34 patients with suspected Cohen syndrome referred for molecular analysis of VPS13B.

Results 14 VPS13B gene mutations were identified in 12 patients, and no mutation was found in 22 patients. The presence of chorioretinal dystrophy (92% vs 32%, p=0.0023), intermittent neutropenia (92% vs 5%, p<0.001), and postnatal microcephaly (100% vs 48%, p=0.0045) was significantly higher in the group of patients with a VPS13B gene mutation compared to the group of patients without a mutation. All patients with VPS13B mutations had chorioretinal dystrophy and/or intermittent neutropenia. The Kolehmainen diagnostic criteria provided 100% sensibility and 77% specificity when applied to this series.

Conclusion From this study and a review of more than 160 genotyped cases from the literature, it is concluded that, given the large size of the gene, VPS13B screening is not indicated in the absence of chorioretinal dystrophy or neutropenia in patients aged over 5 years. The follow-up of young patients could be a satisfactory alternative unless there are some reproductive issues.

  • Cohen syndrome
  • VPS13B gene
  • neutropenia
  • chorioretinal dystrophy
  • diagnostics tests
  • clinical genetics

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  • Competing interests None.

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.