A novel M163L mutation in connexin 26 causing cell death and associated with autosomal dominant hearing loss.
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.
Matos
T D
TD
Centro de Genética e Biologia Molecular, Faculdade de Ciências da Universidade de Lisboa, 1749-016 Lisboa, Portugal.
Caria
H
H
Simões-Teixeira
H
H
Aasen
T
T
Dias
O
O
Andrea
M
M
Kelsell
D P
DP
Fialho
G
G
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
D017630:Connexins; C000607042:GJB2 protein, human; D011993:Recombinant Fusion Proteins; D000072259:Connexin 26