title: Otopalatodigital spectrum disorders: refinement of the phenotypic and mutational spectrum.
abstract: 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.
authors.affiliation: CHU Bordeaux, Hôpital Pellegrin, Department of Medical Genetics, Centre de Référence des Anomalies du Développement Embryonnaire, Bordeaux cedex, France.|Université de Bordeaux, INSERM U1211, Laboratoire Maladies Rares: Génétique et Métabolisme, Bordeaux, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Moutton
authors.affiliation: CHU Bordeaux, Hôpital Pellegrin, Department of Medical Genetics, Centre de Référence des Anomalies du Développement Embryonnaire, Bordeaux cedex, France.|Université de Bordeaux, INSERM U1211, Laboratoire Maladies Rares: Génétique et Métabolisme, Bordeaux, France.|Plateforme Génome Transcriptome, Centre de Génomique Fonctionnelle de Bordeaux, Université de Bordeaux, Bordeaux, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fergelot
authors.affiliation: CHU Bordeaux, Hôpital Pellegrin, Department of Medical Genetics, Centre de Référence des Anomalies du Développement Embryonnaire, Bordeaux cedex, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Naudion
authors.affiliation: CHU Lyon, Hôpital Femme-Mère-Enfant, Department of Medical Genetics, Bron cedex, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Cordier
authors.affiliation: Université de Bordeaux, INSERM U1211, Laboratoire Maladies Rares: Génétique et Métabolisme, Bordeaux, France.|CHU Bordeaux, Hôpital Pellegrin, Department of Neurology, Fédération des Neurosciences Cliniques, Bordeaux, France.
authors.forename: Guilhem
authors.initials: G
authors.lastname: Solé
authors.affiliation: Université de Bordeaux, INSERM U1211, Laboratoire Maladies Rares: Génétique et Métabolisme, Bordeaux, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Guerineau
authors.affiliation: Plateforme Génome Transcriptome, Centre de Génomique Fonctionnelle de Bordeaux, Université de Bordeaux, Bordeaux, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Hubert
authors.affiliation: CHU Bordeaux, Hôpital Pellegrin, Department of Medical Genetics, Centre de Référence des Anomalies du Développement Embryonnaire, Bordeaux cedex, France.|Université de Bordeaux, INSERM U1211, Laboratoire Maladies Rares: Génétique et Métabolisme, Bordeaux, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Rooryck
authors.affiliation: CHU Bordeaux, Hôpital Pellegrin, Department of Medical Genetics, Centre de Référence des Anomalies du Développement Embryonnaire, Bordeaux cedex, France.|Université de Bordeaux, INSERM U1211, Laboratoire Maladies Rares: Génétique et Métabolisme, Bordeaux, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Vuillaume
authors.affiliation: CHU Bordeaux, Hôpital Pellegrin, Department of Medical Genetics, Centre de Référence des Anomalies du Développement Embryonnaire, Bordeaux cedex, France.|Université de Bordeaux, INSERM U1211, Laboratoire Maladies Rares: Génétique et Métabolisme, Bordeaux, France.
authors.forename: Nada
authors.initials: N
authors.lastname: Houcinat
authors.affiliation: CHU Bordeaux, Hôpital Pellegrin, Department of Medical Genetics, Centre de Référence des Anomalies du Développement Embryonnaire, Bordeaux cedex, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Deforges
authors.affiliation: CHU Bordeaux, Hôpital Pellegrin, Department of Medical Genetics, Centre de Référence des Anomalies du Développement Embryonnaire, Bordeaux cedex, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Bouron
authors.affiliation: CHU Bordeaux, Hôpital Pellegrin, Department of Medical Genetics, Centre de Référence des Anomalies du Développement Embryonnaire, Bordeaux cedex, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Devès
authors.affiliation: Institut Imagine, Hôpital Necker Enfants Malades, Department of Medical Genetics, INSERM U781, Université Paris Descartes-Sorbonne Paris Cité, Paris cedex, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Le Merrer
authors.affiliation: CHU Nantes, Hôpital Mère-Enfant, Department of Medical Genetics, Nantes cedex, France.
authors.forename: Albert
authors.initials: A
authors.lastname: David
authors.affiliation: CHRU Montpellier, Hôpital Arnaud de Villeneuve, Department of Medical Genetics, Université Montpellier INSERM U1183, CLAD Sud Languedoc-Roussillon, Montpellier cedex, France.
authors.forename: David
authors.initials: D
authors.lastname: Geneviève
authors.affiliation: CHU Nice, Hôpital l'Archet 2, Department of Medical Genetics, Nice cedex, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Giuliano
authors.affiliation: Centre Hospitalier Bretagne Atlantique, Department of Medical Genetics and Oncogenetics, Vannes cedex, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Journel
authors.affiliation: Al-Jawhara Center, Department of Medical Genetics, Arabian Gulf University, Manama, Kingdom of Bahrain.
authors.forename: André
authors.initials: A
authors.lastname: Megarbane
authors.affiliation: CHU Dijon, Department of Medical Genetics, Centre de Référence Anomalies de Développement et Syndromes Malformatifs de l'inter-région Grand-Est, Hôpital d'Enfants, Dijon, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.affiliation: CHU Toulouse, Hôpital Purpan, Department of Medical Genetics, UDEAR, Université de Toulouse, Inserm, UPS, CNRS, Toulouse cedex, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chassaing
authors.affiliation: CHU Clermont-Ferrand, Hôpital d'Estaing, Department of Medical Genetics, Clermont-Ferrand cedex, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Francannet
authors.affiliation: CHU de Fort de France, Hôpital Pierre Zobda-Quitman, Department of Neuropediatrics, Centre de Référence Caribéen des Maladies Rares Neurologiques et Neuromusculaires, Martinique, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Sarrazin
authors.affiliation: Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Eva-Lena
authors.initials: EL
authors.lastname: Stattin
authors.affiliation: CHU Nancy, Maternité Régionale Adolphe Pinard, Department of Medical Genetics, Nancy cedex, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Vigneron
authors.affiliation: CHU Raymond Poincaré, Department of Physical Medicine and Rehabilitation, Centre de Référence Maladies Neuromusculaires, Garches, France.
authors.forename: Danielle
authors.initials: D
authors.lastname: Leclair
authors.affiliation: CHRU Montpellier, Hôpital Arnaud de Villeneuve, Department of Medical Genetics, Université Montpellier INSERM U1183, CLAD Sud Languedoc-Roussillon, Montpellier cedex, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Abadie
authors.affiliation: CHRU Montpellier, Hôpital Arnaud de Villeneuve, Department of Medical Genetics, Université Montpellier INSERM U1183, CLAD Sud Languedoc-Roussillon, Montpellier cedex, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sarda
authors.affiliation: AP-HP, Hôpital Robert Debré, Department of Medical Genetics, CLAD Ile de France, Paris, France.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Baumann
authors.affiliation: CHU Bordeaux, Hôpital Pellegrin, Department of Medical Genetics, Centre de Référence des Anomalies du Développement Embryonnaire, Bordeaux cedex, France.
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Delrue
authors.affiliation: CHU Bordeaux, Hôpital Pellegrin, Department of Medical Genetics, Centre de Référence des Anomalies du Développement Embryonnaire, Bordeaux cedex, France.|Université de Bordeaux, INSERM U1211, Laboratoire Maladies Rares: Génétique et Métabolisme, Bordeaux, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Arveiler
authors.affiliation: CHU Bordeaux, Hôpital Pellegrin, Department of Medical Genetics, Centre de Référence des Anomalies du Développement Embryonnaire, Bordeaux cedex, France.|Université de Bordeaux, INSERM U1211, Laboratoire Maladies Rares: Génétique et Métabolisme, Bordeaux, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.affiliation: CHU Bordeaux, Hôpital Pellegrin, Department of Medical Genetics, Centre de Référence des Anomalies du Développement Embryonnaire, Bordeaux cedex, France.|Université de Bordeaux, INSERM U1211, Laboratoire Maladies Rares: Génétique et Métabolisme, Bordeaux, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Goizet
authors.affiliation: Université de Bordeaux, INSERM U1211, Laboratoire Maladies Rares: Génétique et Métabolisme, Bordeaux, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coupry
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D019465:Craniofacial Abnormalities / Q000175:diagnosis* / Q000235:genetics*; D005091:Exons; D019066:Facies; D005260:Female; D064448:Filamins / Q000235:genetics; D056726:Genetic Association Studies; D006228:Hand Deformities, Congenital / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000175:diagnosis* / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017422:Sequence Analysis, DNA
chemical_list: C578663:FLNA protein, human; D064448:Filamins