Application of whole-exome sequencing to unravel the molecular basis of undiagnosed syndromic congenital neutropenia with intellectual disability - Université de Bourgogne Accéder directement au contenu
Article Dans Une Revue American Journal of Medical Genetics Part A Année : 2016

Application of whole-exome sequencing to unravel the molecular basis of undiagnosed syndromic congenital neutropenia with intellectual disability

Alexandra Gauthier-Vasserot
  • Fonction : Auteur
Christel Thauvin-Robinet
  • Fonction : Auteur
  • PersonId : 889819
Ange-Line Bruel
  • Fonction : Auteur
  • PersonId : 994768
Yannis Duffourd
  • Fonction : Auteur
  • PersonId : 994654
Judith Saint-Onge
  • Fonction : Auteur
  • PersonId : 994653
Thibaut Jouan
  • Fonction : Auteur
  • PersonId : 995276
Jean-Baptiste Rivière
  • Fonction : Auteur
  • PersonId : 994656
Delphine Heron
  • Fonction : Auteur
  • PersonId : 906967
Jean Donadieu
  • Fonction : Auteur
  • PersonId : 852867
Christine Bellanné-Chantelot
Claire Briandet
  • Fonction : Auteur
Frédéric Huet
  • Fonction : Auteur
  • PersonId : 893243
Paul Kuentz
  • Fonction : Auteur
  • PersonId : 995003
Daphné Lehalle
Laurence Duplomb-Jego
  • Fonction : Auteur
  • PersonId : 994669
Elodie Gautier
  • Fonction : Auteur
Isabelle Maystadt
  • Fonction : Auteur
Lucile Pinson
  • Fonction : Auteur
Daniel Amram
  • Fonction : Auteur
Salima El Chehadeh
Judith Melki
  • Fonction : Auteur
  • PersonId : 931056
Sophia Julia
  • Fonction : Auteur
Laurence Faivre
  • Fonction : Auteur
  • PersonId : 856301
Julien Thevenon
  • Fonction : Auteur
  • PersonId : 964270

Résumé

Neutropenia can be qualified as congenital when of neonatal onset or when associated with extra-hematopoietic manifestations. Overall, 30% of patients with congenital neutropenia (CN) remain without a molecular diagnosis after a multidisciplinary consultation and tedious diagnostic strategy. In the rare situations when neutropenia is identified and associated with intellectual disability (ID), there are few diagnostic hypotheses to test. This retrospective multicenter study reports on a clinically heterogeneous cohort of 10 unrelated patients with CN associated with ID and no molecular diagnosis prior to whole-exome sequencing (WES). WES provided a diagnostic yield of 40% (4/10). The results suggested that in many cases neutropenia and syndromic manifestations could not be assigned to the same molecular alteration. Three sub-groups of patients were highlighted: (i) severe, symptomatic chronic neutropenia, detected early in life, and related to a known mutation in the CN spectrum (ELANE); (ii) mild to moderate benign intermittent neutropenia, detected later, and associated with mutations in genes implicated in neurodevelopmental disorders (CHD2, HUWE1); and (iii) moderate to severe intermittent neutropenia as a probably undiagnosed feature of a newly reported syndrome (KAT6A). Unlike KAT6A, which seems to be associated with a syndromic form of CN, the other reported mutations may not explain the entire clinical picture. Although targeted gene sequencing can be discussed for the primary diagnosis of severe CN, we suggest that performing WES for the diagnosis of disorders associating CN with ID will not only provide the etiological diagnosis but will also pave the way towards personalized care and follow-up. (C) 2016 Wiley Periodicals, Inc., (C) 2016 John Wiley & Sons, Ltd

Mots clés

Fichier non déposé

Dates et versions

hal-01410416 , version 1 (06-12-2016)

Identifiants

Citer

Alexandra Gauthier-Vasserot, Christel Thauvin-Robinet, Ange-Line Bruel, Yannis Duffourd, Judith Saint-Onge, et al.. Application of whole-exome sequencing to unravel the molecular basis of undiagnosed syndromic congenital neutropenia with intellectual disability. American Journal of Medical Genetics Part A, 2016, ⟨10.1002/ajmg.a.37969⟩. ⟨hal-01410416⟩
122 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More