title: 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.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Hôpital d'Enfants, CHU Dijon, Université de Dijon, France.
authors.forename: Salima
authors.initials: S
authors.lastname: El Chehadeh
authors.forename: Bernard
authors.initials: B
authors.lastname: Aral
authors.forename: Nadège
authors.initials: N
authors.lastname: Gigot
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.forename: Anne
authors.initials: A
authors.lastname: Donzel
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Delrue
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.forename: Albert
authors.initials: A
authors.lastname: David
authors.forename: Lydie
authors.initials: L
authors.lastname: Burglen
authors.forename: Nicole
authors.initials: N
authors.lastname: Philip
authors.forename: Anne
authors.initials: A
authors.lastname: Moncla
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: Marlène
authors.initials: M
authors.lastname: Rio
authors.forename: Patrick
authors.initials: P
authors.lastname: Edery
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonneau
authors.forename: Alexandra
authors.initials: A
authors.lastname: Afenjar
authors.forename: Aurélia
authors.initials: A
authors.lastname: Jacquette
authors.forename: Delphine
authors.initials: D
authors.lastname: Heron
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarda
authors.forename: Lucile
authors.initials: L
authors.lastname: Pinson
authors.forename: Bérénice
authors.initials: B
authors.lastname: Doray
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Vigneron
authors.forename: Bruno
authors.initials: B
authors.lastname: Leheup
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Frances-Guidet
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: Dienne
authors.forename: Muriel
authors.initials: M
authors.lastname: Holder
authors.forename: Alice
authors.initials: A
authors.lastname: Masurel-Paulet
authors.forename: Frédéric
authors.initials: F
authors.lastname: Huet
authors.forename: Jean-Raymond
authors.initials: JR
authors.lastname: Teyssier
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009503:Neutropenia / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D015203:Reproducibility of Results; D012164:Retinal Diseases / Q000150:complications / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D013577:Syndrome; D033921:Vesicular Transport Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: C475722:VPS13B protein, human; D033921:Vesicular Transport Proteins