Otopalatodigital spectrum disorders: refinement of the phenotypic and mutational spectrum.

Fiche publication


Date publication

août 2016

Journal

Journal of human genetics

Auteurs

Membres identifiés du Cancéropôle Est :
Pr FAIVRE Laurence


Tous les auteurs :
Moutton S, Fergelot P, Naudion S, Cordier MP, Solé G, Guerineau E, Hubert C, Rooryck C, Vuillaume ML, Houcinat N, Deforges J, Bouron J, Devès S, Le Merrer M, David A, Geneviève D, Giuliano F, Journel H, Megarbane A, Faivre L, Chassaing N, Francannet C, Sarrazin E, Stattin EL, Vigneron J, Leclair D, Abadie C, Sarda P, Baumann C, Delrue MA, Arveiler B, Lacombe D, Goizet C, Coupry I

Résumé

Otopalatodigital spectrum disorders (OPDSD) constitute a group of dominant X-linked osteochondrodysplasias including four syndromes: otopalatodigital syndromes type 1 and type 2 (OPD1 and OPD2), frontometaphyseal dysplasia, and Melnick-Needles syndrome. These syndromes variably associate specific facial and extremities features, hearing loss, cleft palate, skeletal dysplasia and several malformations, and show important clinical overlap over the different entities. FLNA gain-of-function mutations were identified in these conditions. FLNA encodes filamin A, a scaffolding actin-binding protein. Here, we report phenotypic descriptions and molecular results of FLNA analysis in a large series of 27 probands hypothesized to be affected by OPDSD. We identified 11 different missense mutations in 15 unrelated probands (n=15/27, 56%), of which seven were novel, including one of unknown significance. Segregation analyses within families made possible investigating 20 additional relatives carrying a mutation. This series allows refining the phenotypic and mutational spectrum of FLNA mutations causing OPDSD, and providing suggestions to avoid the overdiagnosis of OPD1.

Mots clés

Alleles, Amino Acid Substitution, Craniofacial Abnormalities, diagnosis, Exons, Facies, Female, Filamins, genetics, Genetic Association Studies, Hand Deformities, Congenital, diagnosis, Humans, Male, Mutation, Osteochondrodysplasias, diagnosis, Pedigree, Phenotype, Sequence Analysis, DNA

Référence

J. Hum. Genet.. 2016 Aug;61(8):693-9