title: A mutation in CCDC50, a gene encoding an effector of epidermal growth factor-mediated cell signaling, causes progressive hearing loss.
abstract: We previously mapped a novel autosomal dominant deafness locus, DFNA44, by studying a family with postlingual, progressive, nonsyndromic hearing loss. We report here on the identification of a mutation in CCDC50 as the cause of hearing loss in the family. CCDC50 encodes Ymer, an effector of epidermal growth factor (EGF)-mediated cell signaling that is ubiquitously expressed in different organs and has been suggested to inhibit down-regulation of the EGF receptor. We have examined its expression pattern in mouse inner ear. Western blotting and cell transfection results indicate that Ymer is a soluble, cytoplasmic protein, and immunostaining shows that Ymer is expressed in a complex spatiotemporal pattern during inner ear development. In adult inner ear, the expression of Ymer is restricted to the pillar cells of the cochlea, the stria vascularis, and the vestibular sensory epithelia, where it shows spatial overlap with the microtubule-based cytoskeleton. In dividing cells, Ymer colocalizes with microtubules of the mitotic apparatus. We suggest that DFNA44 hearing loss may result from a time-dependent disorganization of the microtubule-based cytoskeleton in the pillar cells and stria vascularis of the adult auditory system.
authors.affiliation: Unidad de Genetica Molecular, Hospital Ramon y Cajal, Madrid, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Modamio-Hoybjor
authors.forename: Angeles
authors.initials: A
authors.lastname: Mencia
authors.forename: Richard
authors.initials: R
authors.lastname: Goodyear
authors.forename: Ignacio
authors.initials: I
authors.lastname: del Castillo
authors.forename: Guy
authors.initials: G
authors.lastname: Richardson
authors.forename: Felipe
authors.initials: F
authors.lastname: Moreno
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Moreno-Pelayo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003051:Cochlea / Q000166:cytology; D003593:Cytoplasm / Q000378:metabolism; D007758:Ear, Inner / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism*; D018069:Hair Cells, Vestibular / Q000378:metabolism; D006367:HeLa Cells; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D041681:NIH 3T3 Cells; D016366:Open Reading Frames; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D012995:Solubility; D013316:Stria Vascularis / Q000378:metabolism; D014162:Transfection; D014722:Vestibule, Labyrinth / Q000166:cytology
chemical_list: C478972:CCDC50 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor