Otopalatodigital spectrum disorders: refinement of the phenotypic and mutational spectrum

Sébastien Moutton (1, 2) , Patricia Fergelot (1, 2, 3) , Sophie Naudion (1) , Marie-Pierre Cordier (4) , Guilhem Solé (2, 5) , Elodie Guerineau (2) , Christophe Hubert (3) , Caroline Rooryck (1, 2) , Marie-Laure Vuillaume (1, 2) , Nada Houcinat (1, 2) , Julie Deforges (1) , Julie Bouron (1) , Sylvie Devès (1) , Martine Le Merrer (6, 7) , Albert David (8) , David Geneviève (9, 10) , Fabienne Giuliano (11) , Hubert Journel (12) , Andre Megarbane (13) , Laurence Faivre (14) , Nicolas Chassaing (15, 16) , Christine Francannet (17) , Elisabeth Sarrazin (18) , Eva-Lena Stattin , Jacqueline Vigneron (19) , Danielle Leclair (20) , Caroline Abadie (9, 10) , Pierre Sarda (9, 10) , Clarisse Baumann (21) , Marie-Ange Delrue (1) , Benoit Arveiler (1, 2) , Didier Lacombe (1, 2) , Cyril Goizet (1, 2) , Isabelle Coupry (2)

1 Service de génétique médicale
2 Maladies rares, génétique et métabolisme / Rare Diseases, Genetics and Metabolism
3 CGFB - Centre Génomique Fonctionnelle Bordeaux [Bordeaux]
4 HFME - Hôpital Femme Mère Enfant [CHU - HCL]
5 Service de neurologie [Bordeaux]
6 Service de Génétique Médicale [CHU Necker]
7 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
8 Service de génétique médicale - Unité de génétique clinique [Nantes]
9 Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier]
10 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
11 Dpt génétique médicale [CHU Nice]
12 CHBA - Centre hospitalier Bretagne Atlantique (Morbihan)
13 Arabian Gulf University
14 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
15 UDEAR - Unité différenciation épidermique et auto-immunité rhumatoïde
16 Service Génétique Médicale [CHU Toulouse]
17 Service de Génétique Médicale [CHU Clermont-Ferrand]
18 Hôpital Pierre Zobda-Quitman [CHU de la Martinique]
19 Service de Génétique Médicale [CHRU Nancy]
20 Service de médecine physique et réadaptation [CHU Raymond-Poincaré]
21 AP-HP Hôpital universitaire Robert-Debré [Paris]

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.

Domaines: Génétique humaine

Sébastien Moutton, Patricia Fergelot, Sophie Naudion, Marie-Pierre Cordier, Guilhem Solé, et al.. Otopalatodigital spectrum disorders: refinement of the phenotypic and mutational spectrum. Journal of Human Genetics, 2016, 61 (8), pp.693 - 699. ⟨10.1038/jhg.2016.37⟩. ⟨hal-01868243⟩