Otopalatodigital spectrum disorders: refinement of the phenotypic and mutational spectrum
2016 (English)In: Journal of Human Genetics, ISSN 1434-5161, E-ISSN 1435-232X, Vol. 61, no 8, 693-699 p.Article in journal (Refereed) Published
Hop Pellegrin, CHU Bordeaux, Dept Med Genet, Ctr Reference Anomalies Dev Embryonnaire, Bordeaux, France.;Univ Bordeaux, INSERM, U1211, Lab Malad Rares Genet & Metab, Bordeaux, France..
Hop Pellegrin, CHU Bordeaux, Dept Med Genet, Ctr Reference Anomalies Dev Embryonnaire, Bordeaux, France.;Univ Bordeaux, INSERM, U1211, Lab Malad Rares Genet & Metab, Bordeaux, France.;Univ Bordeaux, Ctr Genom Fonct Bordeaux, Plateforme Genome Transcriptome, Bordeaux, France..
Hop Pellegrin, CHU Bordeaux, Dept Med Genet, Ctr Reference Anomalies Dev Embryonnaire, Bordeaux, France..
Hop Femme Mere Enfant, CHU Lyon, Dept Med Genet, Bron, France..
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.
Place, publisher, year, edition, pages
2016. Vol. 61, no 8, 693-699 p.
IdentifiersURN: urn:nbn:se:uu:diva-304432DOI: 10.1038/jhg.2016.37ISI: 000382432300004PubMedID: 27193221OAI: oai:DiVA.org:uu-304432DiVA: diva2:1033129