title: The novel R75Q mutation in the GJB2 gene causes autosomal dominant hearing loss and palmoplantar keratoderma in a Turkish family.
abstract: Dominant mutations in the GJB2 gene encoding connexin 26 (Cx26) can cause non-syndromic hearing impairment alone or in association with palmoplantar keratoderma (PPK). We have identified the novel G224A (R75Q) mutation in the GJB2 gene in a four-generation family from Turkey with autosomal dominant inherited hearing impairment and PPK. The age of onset and progression of hearing loss were found to be variable among affected family members, but all of them had more severe impairment at higher hearing frequencies. Interestingly, the novel R75Q mutation affects the same amino acid residue as described recently in a small family (R75W) with profound prelingual hearing loss and PPK. However, the R75W mutation was also observed in a control individual without PPK and unknown hearing status. Therefore, the nature of the R75W mutation remains ambiguous. Our molecular findings provide further evidence for the importance of the conserved R75 in Cx26 for the physiological function of the inner ear and the epidermal cells of the skin.
authors.affiliation: Division of Medical Genetics, Child Health Institute, Istanbul University, Istanbul, Turkey.
authors.forename: O
authors.initials: O
authors.lastname: Uyguner
authors.forename: T
authors.initials: T
authors.lastname: Tukel
authors.forename: C
authors.initials: C
authors.lastname: Baykal
authors.forename: H
authors.initials: H
authors.lastname: Eris
authors.forename: M
authors.initials: M
authors.lastname: Emiroglu
authors.forename: G
authors.initials: G
authors.lastname: Hafiz
authors.forename: A
authors.initials: A
authors.lastname: Ghanbari
authors.forename: N
authors.initials: N
authors.lastname: Baserer
authors.forename: M
authors.initials: M
authors.lastname: Yuksel-Apak
authors.forename: B
authors.initials: B
authors.lastname: Wollnik
mesh_terms: D019943:Amino Acid Substitution; D001120:Arginine / Q000235:genetics; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D018698:Glutamic Acid / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007645:Keratoderma, Palmoplantar / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D014421:Turkey
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D018698:Glutamic Acid; D001120:Arginine