title: Fetal phenotypes in otopalatodigital spectrum disorders.
abstract: Otopalatodigital spectrum disorders (OPDSD) include OPD syndromes types 1 and type 2 (OPD1, OPD2), Melnick-Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). These conditions are clinically characterized by variable skeletal dysplasia associated in males, with extra-skeletal features including brain malformations, cleft palate, cardiac anomalies, omphalocele and obstructive uropathy. Mutations in the FLNA gene have been reported in most FMD and OPD2 cases and in all instances of typical OPD1 and MNS. Here, we report a series of 10 fetuses and a neonatally deceased newborn displaying a multiple congenital anomalies syndrome suggestive of OPDSD and in whom we performed FLNA analysis. We found a global mutation rate of 44%. This series allows expanding the clinical and FLNA mutational spectrum in OPDSD. However, we emphasize difficulties to correctly discriminate OPDSD based on clinical criteria in fetuses due to the major overlap between these conditions. Molecular analyses may help pathologists to refine clinical diagnosis according to the type and the location of FLNA mutations. Discriminating the type of OPDSD is of importance in order to improve the genetic counseling to provide to families.
authors.affiliation: CHU Bordeaux, Centre de Référence des Anomalies du Développement Embryonnaire, Service de Génétique Médicale, Bordeaux, France.
authors.forename: S
authors.initials: S
authors.lastname: Naudion
authors.affiliation: CHU Bordeaux, Centre de Référence des Anomalies du Développement Embryonnaire, Service de Génétique Médicale, Bordeaux, France.|University Bordeaux, Laboratoire Maladies Rares, Génétique et Métabolisme (MRGM), Bordeaux, France.
authors.forename: S
authors.initials: S
authors.lastname: Moutton
authors.affiliation: University Bordeaux, Laboratoire Maladies Rares, Génétique et Métabolisme (MRGM), Bordeaux, France.
authors.forename: I
authors.initials: I
authors.lastname: Coupry
authors.affiliation: University Bordeaux, Laboratoire Maladies Rares, Génétique et Métabolisme (MRGM), Bordeaux, France.|CHU Bordeaux, Fédération des Neurosciences Cliniques, Bordeaux, France.
authors.forename: G
authors.initials: G
authors.lastname: Sole
authors.affiliation: CHU Bordeaux, Centre de Référence des Anomalies du Développement Embryonnaire, Service de Génétique Médicale, Bordeaux, France.
authors.forename: J
authors.initials: J
authors.lastname: Deforges
authors.affiliation: University Bordeaux, Laboratoire Maladies Rares, Génétique et Métabolisme (MRGM), Bordeaux, France.
authors.forename: E
authors.initials: E
authors.lastname: Guerineau
authors.affiliation: Plateforme Génome Transcriptome, Centre de Génomique Fonctionnelle de Bordeaux, Université de Bordeaux, Bordeaux, France.
authors.forename: C
authors.initials: C
authors.lastname: Hubert
authors.affiliation: CHU Bordeaux, Centre de Référence des Anomalies du Développement Embryonnaire, Service de Génétique Médicale, Bordeaux, France.
authors.forename: S
authors.initials: S
authors.lastname: Deves
authors.affiliation: University Bordeaux, Laboratoire Maladies Rares, Génétique et Métabolisme (MRGM), Bordeaux, France.
authors.forename: J
authors.initials: J
authors.lastname: Pilliod
authors.affiliation: CHU Bordeaux, Centre de Référence des Anomalies du Développement Embryonnaire, Service de Génétique Médicale, Bordeaux, France.|University Bordeaux, Laboratoire Maladies Rares, Génétique et Métabolisme (MRGM), Bordeaux, France.
authors.forename: C
authors.initials: C
authors.lastname: Rooryck
authors.affiliation: CHU Lyon, Service de Génétique, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Abel
authors.affiliation: CHU Lyon, Service de Pathologie du Nord, Hôpital de la Croix-Rousse, Lyon, France.
authors.forename: F
authors.initials: F
authors.lastname: Le Breton
authors.affiliation: CHU de Lyon, Centre de Pathologie Est, Hospices Civils de Lyon, Lyon, France.
authors.forename: S
authors.initials: S
authors.lastname: Collardeau-Frachon
authors.affiliation: CHU Lyon, Service de Génétique Médicale, Hôpital Mère Enfant, Lyon, France.
authors.forename: M P
authors.initials: MP
authors.lastname: Cordier
authors.affiliation: APHP, Service de Biologie du Développement, Hôpital Robert Debré, Paris, France.
authors.forename: A L
authors.initials: AL
authors.lastname: Delezoide
authors.affiliation: CHU Rouen, Service de Génétique Médicale, Rouen, France.
authors.forename: A
authors.initials: A
authors.lastname: Goldenberg
authors.affiliation: CHU Rennes, Service d'Anatomie Cytologie Pathologique, Rennes, France.
authors.forename: P
authors.initials: P
authors.lastname: Loget
authors.affiliation: INSERM U78, Laboratoire de Neurogénétique Moléculaire, Université de Paris XI, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Melki
authors.affiliation: CHU de Rennes, Service de Génétique Clinique, Centre de Référence Anomalies du Développement CLAD-Ouest, Hôpital Sud, Rennes, France.
authors.forename: S
authors.initials: S
authors.lastname: Odent
authors.affiliation: CHU Rouen, Service d'Anatomie Pathologique, Rouen, France.
authors.forename: S
authors.initials: S
authors.lastname: Patrier
authors.affiliation: Département de Génétique, APHP-Hôpital universitaire Robert Debré, Université Sorbonne Paris-Cité, Faculté de Médecine Denis Diderot-Paris 7, and INSERM UMR 1141, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Verloes
authors.affiliation: APHP, Service de Génétique Médicale, Maternité Port-Royal, Paris, France.
authors.forename: G
authors.initials: G
authors.lastname: Viot
authors.affiliation: CHRU Tours, Service de Génétique, Hôpital Bretonneau, Tours, France.
authors.forename: S
authors.initials: S
authors.lastname: Blesson
authors.affiliation: APHP, Service Histo-Embryologie et Cytogénétique, Hôpital Necker, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Bessières
authors.affiliation: CHU Bordeaux, Centre de Référence des Anomalies du Développement Embryonnaire, Service de Génétique Médicale, Bordeaux, France.|University Bordeaux, Laboratoire Maladies Rares, Génétique et Métabolisme (MRGM), Bordeaux, France.
authors.forename: D
authors.initials: D
authors.lastname: Lacombe
authors.affiliation: CHU Bordeaux, Centre de Référence des Anomalies du Développement Embryonnaire, Service de Génétique Médicale, Bordeaux, France.|University Bordeaux, Laboratoire Maladies Rares, Génétique et Métabolisme (MRGM), Bordeaux, France.
authors.forename: B
authors.initials: B
authors.lastname: Arveiler
authors.affiliation: CHU Bordeaux, Centre de Référence des Anomalies du Développement Embryonnaire, Service de Génétique Médicale, Bordeaux, France.|University Bordeaux, Laboratoire Maladies Rares, Génétique et Métabolisme (MRGM), Bordeaux, France.
authors.forename: C
authors.initials: C
authors.lastname: Goizet
authors.affiliation: CHU Bordeaux, Centre de Référence des Anomalies du Développement Embryonnaire, Service de Génétique Médicale, Bordeaux, France.|University Bordeaux, Laboratoire Maladies Rares, Génétique et Métabolisme (MRGM), Bordeaux, France.|Plateforme Génome Transcriptome, Centre de Génomique Fonctionnelle de Bordeaux, Université de Bordeaux, Bordeaux, France.
authors.forename: P
authors.initials: P
authors.lastname: Fergelot
mesh_terms: D019465:Craniofacial Abnormalities / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005333:Fetus; D064448:Filamins / Q000235:genetics*; D006228:Hand Deformities, Congenital / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype
chemical_list: C578663:FLNA protein, human; D064448:Filamins
keywords: FLNA; FMD; MNS; Melnick-Needles; OPD2; Otopalatodigital; filamin A; frontometaphyseal dysplasia