We determined the occurrence of c.-259C>T in cases of non-syndromic hearing impairment lacking known pathogenic alterations in GJB2 (n = 43), a non-syndromic hearing impaired patient group (n = 15) bearing the heterozygous GJB2 mutations c.35delG, c.[79G>A];[341A>G] (p. [V27I];[E114G]), c.109G>A (p.V37I), c.154G>C (p.V52L), c.262G>T (p.A88S), c.269T>C (p.L90P) and c.551G>C (p.R184P) and in a normal hearing group lacking alterations in GJB2 (n = 50).
It was also revealed that subjects carrying either c.[79G>A; 341A>G]+[79G>A; 341A>G] or c.[109G>A]+[79G>A; 341A>G] had significantly fewer cases of severe HI than the reference group of homozygous c.235delC, whereas the subjects carrying c.[235delC]+[176_191del16] had more cases of severe HI than the homozygous c.235delC group.
The haplotypes composed of rs2274084 and rs2274083 suggested that C-C may be a risk haplotype for the sporadic hearing impairment while T-T may be protective against hearing impairment.
Our findings provide further evidence of a correlation between the p.R75Q mutation in Cx26 and a syndromic hearing impairment with palmoplantar keratoderma.
The haplotypes composed of rs2274084 and rs2274083 suggested that C-C may be a risk haplotype for the sporadic hearing impairment while T-T may be protective against hearing impairment.
However, the lack of correlation in the severity and age-of-onset in hearing impairment with homozygous or heterozygous G79A or G109A or combination of both variants in the GJB2 gene in those subjects with hearing impairment and normal hearing indicates that those variants of GJB2 gene may not be a modifier of the phenotypic effects of the T7511C mutation in those subjects.
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.
A total of 81.37% of patients harboured at least one c.35delG allele; c.167delT and c.-23 + 1G> A were identified in 10.78% and the 9.8% of patients respectively; c.35delG homozygotes presented more severe hearing impairment (75.59% of profound hearing loss) and a higher mean PTA0.25-4 kHz (96.79 ± 21.11 dB HL) with respect to c.35delG/non-c.35delG and c.35delG/Wt patients (P < 0.05).