title: A novel M163L mutation in connexin 26 causing cell death and associated with autosomal dominant hearing loss.
abstract: Mutations in GJB2 gene (encoding connexin 26) are the most common cause of hereditary non-syndromic sensorineural hearing loss (NSSHL) in different populations. The majority of GJB2 mutations are recessive, but a few dominant mutations have been associated with hearing loss either isolated or associated with skin disease. We describe a novel dominant pathogenic GJB2 mutation, identified in a Portuguese family affected with bilateral mild/moderate high-frequency NSSHL. In vitro functional studies demonstrate that the mutant protein (p.M163L) has defective trafficking to the plasma membrane and is associated with increased cell death.
authors.affiliation: Centro de Genética e Biologia Molecular, Faculdade de Ciências da Universidade de Lisboa, 1749-016 Lisboa, Portugal.
authors.forename: T D
authors.initials: TD
authors.lastname: Matos
authors.forename: H
authors.initials: H
authors.lastname: Caria
authors.forename: H
authors.initials: H
authors.lastname: Simões-Teixeira
authors.forename: T
authors.initials: T
authors.lastname: Aasen
authors.forename: O
authors.initials: O
authors.lastname: Dias
authors.forename: M
authors.initials: M
authors.lastname: Andrea
authors.forename: D P
authors.initials: DP
authors.lastname: Kelsell
authors.forename: G
authors.initials: G
authors.lastname: Fialho
mesh_terms: D001299:Audiometry; D016923:Cell Death; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D011993:Recombinant Fusion Proteins; D000072259:Connexin 26