Otopalatodigital spectrum disorders: refinement of the phenotypic and mutational spectrum.
J Hum Genet. 2016-05-19; 61(8): 693-699
DOI: 10.1038/jhg.2016.37
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1. J Hum Genet. 2016 Aug;61(8):693-9. doi: 10.1038/jhg.2016.37. Epub 2016 May 19.
Otopalatodigital spectrum disorders: refinement of the phenotypic and mutational
spectrum.
Moutton S(1)(2), Fergelot P(1)(2)(3), Naudion S(1), Cordier MP(4), Solé G(2)(5),
Guerineau E(2), Hubert C(3), Rooryck C(1)(2), Vuillaume ML(1)(2), Houcinat
N(1)(2), Deforges J(1), Bouron J(1), Devès S(1), Le Merrer M(6), David A(7),
Geneviève D(8), Giuliano F(9), Journel H(10), Megarbane A(11), Faivre L(12),
Chassaing N(13), Francannet C(14), Sarrazin E(15), Stattin EL(16), Vigneron
J(17), Leclair D(18), Abadie C(8), Sarda P(8), Baumann C(19), Delrue MA(1),
Arveiler B(1)(2), Lacombe D(1)(2), Goizet C(1)(2), Coupry I(2).
Author information:
(1)CHU Bordeaux, Hôpital Pellegrin, Department of Medical Genetics, Centre de
Référence des Anomalies du Développement Embryonnaire, Bordeaux cedex, France.
(2)Université de Bordeaux, INSERM U1211, Laboratoire Maladies Rares: Génétique et
Métabolisme, Bordeaux, France.
(3)Plateforme Génome Transcriptome, Centre de Génomique Fonctionnelle de
Bordeaux, Université de Bordeaux, Bordeaux, France.
(4)CHU Lyon, Hôpital Femme-Mère-Enfant, Department of Medical Genetics, Bron
cedex, France.
(5)CHU Bordeaux, Hôpital Pellegrin, Department of Neurology, Fédération des
Neurosciences Cliniques, Bordeaux, France.
(6)Institut Imagine, Hôpital Necker Enfants Malades, Department of Medical
Genetics, INSERM U781, Université Paris Descartes-Sorbonne Paris Cité, Paris
cedex, France.
(7)CHU Nantes, Hôpital Mère-Enfant, Department of Medical Genetics, Nantes cedex,
France.
(8)CHRU Montpellier, Hôpital Arnaud de Villeneuve, Department of Medical
Genetics, Université Montpellier INSERM U1183, CLAD Sud Languedoc-Roussillon,
Montpellier cedex, France.
(9)CHU Nice, Hôpital l’Archet 2, Department of Medical Genetics, Nice cedex,
France.
(10)Centre Hospitalier Bretagne Atlantique, Department of Medical Genetics and
Oncogenetics, Vannes cedex, France.
(11)Al-Jawhara Center, Department of Medical Genetics, Arabian Gulf University,
Manama, Kingdom of Bahrain.
(12)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.
(13)CHU Toulouse, Hôpital Purpan, Department of Medical Genetics, UDEAR,
Université de Toulouse, Inserm, UPS, CNRS, Toulouse cedex, France.
(14)CHU Clermont-Ferrand, Hôpital d’Estaing, Department of Medical Genetics,
Clermont-Ferrand cedex, France.
(15)CHU de Fort de France, Hôpital Pierre Zobda-Quitman, Department of
Neuropediatrics, Centre de Référence Caribéen des Maladies Rares Neurologiques et
Neuromusculaires, Martinique, France.
(16)Department of Immunology, Genetics and Pathology, Science for Life
Laboratory, Uppsala University, Uppsala, Sweden.
(17)CHU Nancy, Maternité Régionale Adolphe Pinard, Department of Medical
Genetics, Nancy cedex, France.
(18)CHU Raymond Poincaré, Department of Physical Medicine and Rehabilitation,
Centre de Référence Maladies Neuromusculaires, Garches, France.
(19)AP-HP, Hôpital Robert Debré, Department of Medical Genetics, CLAD Ile de
France, Paris, 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.
DOI: 10.1038/jhg.2016.37
PMID: 27193221 [Indexed for MEDLINE]