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.

Non-syndromic hearing impairment in a multi-ethnic population of Northeastern Brazil

“…In these cases an AD mode of inheritance was observed, and in some subjects the HI was associated with palmoplantar keratoderma [58,59]. An AD mode of inheritance appeared probable in the present study in which 10 members of a family with no reported consanguinity had HI, three of whom also had palmoplantar keratoderma.…”

“…The p.R75Q (OMIM, img 121011.0026) mutation has variously been described in subjects with HI in Turkey [58], France [59], a family of Russian origin [60], and in 1/207 patients in Brazil [8]. In these cases an AD mode of inheritance was observed, and in some subjects the HI was associated with palmoplantar keratoderma [58,59].…”

Assembly of the cochlear gap junction macromolecular complex requires connexin 26

“…Interestingly, these cell lines clearly showed functional differences in neurobiotin (NB) transfer analysis ( Figure 4, I, J, O, and P) depending on the level of GJP disruption (Figure 4, F, G, L, and M), even when mutations at the same amino acid in CX26 were used (i.e., R75W and R75Q, which also cause hereditary deafness; ref. 24). The cells with smaller GJPs had less extensive NB dye transfer as compared with cells with larger GJPs (Figure 4, H-Q).…”

Review Studies of GJB2 Gene in Patients with Hearing Impairment in Pakistan

“…The most prevalent nonsense mutation W24X truncating Cx26 protein (24 amino acids), was first reported in a Pakistani family [65]. The GJB2 mutations which cause syndromic HL include: delE42, [67], G12R, D50N and S17F [68], G59A [69], N54K [70], R75Q [71], R75W [72], D66H [73], G130V [74]. While autosomal dominant non-syndromic HL is caused by C202F [75], R143Q [76], W44C [77], R184Q [78], D179N [79] and G21R gene mutation.…”