title: A novel filamin A D203Y mutation in a female patient with otopalatodigital type 1 syndrome and extremely skewed X chromosome inactivation.
abstract: Otopalatodigital syndrome type 1 (OPD1) [OMIM 311300] is an X-linked dominant multiple congenital anomalies disease mainly characterized by a generalized skeletal dysplasia, mild mental retardation, hearing loss, cleft palate, and typical facial anomalies. OPD1 belongs to a group of X-linked skeletal dysplasias known as oto-palato-digital syndrome spectrum disorders that also include OPD2, Melnick-Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). Recently, it has been demonstrated that mutations in the gene encoding the cytoskeletal protein Filamin A (FLNA) are responsible for this group of clinically overlapping human syndromes. We present the phenotypic and molecular data of a sporadic female patient clinically diagnosed with an OPD1 syndrome who carried a novel FLNA point mutation resulting in an Asp203Tyr substitution in the actin-binding domain of the protein. X-inactivation analyses demonstrated an extremely skewed pattern towards her maternal chromosome. Our results add to the molecular spectrum of the oto-palato-digital related syndromes and contribute to the delineation of phenotype-genotype correlation in this group of X-linked skeletal disorders.
authors.affiliation: Department of Genetics, Hospital General de Mexico-Facultad de Medicina, UNAM, Mexico City.
authors.forename: Alberto
authors.initials: A
authors.lastname: Hidalgo-Bravo
authors.forename: Ericka N
authors.initials: EN
authors.lastname: Pompa-Mera
authors.forename: Susana
authors.initials: S
authors.lastname: Kofman-Alfaro
authors.forename: Cesar R
authors.initials: CR
authors.lastname: Gonzalez-Bonilla
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Zenteno
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000328:Adult; D001483:Base Sequence; D001848:Bone Diseases, Developmental / Q000473:pathology; D041321:Chromosomes, Human, X / Q000235:genetics*; D002972:Cleft Palate / Q000473:pathology; D003285:Contractile Proteins / Q000235:genetics*; D019465:Craniofacial Abnormalities; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004303:Dosage Compensation, Genetic; D005260:Female; D064448:Filamins; D006130:Growth Disorders / Q000473:pathology; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics*; D020125:Mutation, Missense; D013576:Syndactyly / Q000473:pathology; D013577:Syndrome
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins; D004247:DNA