Mutations of GJB2 encoding connexin 26 contribute to non-syndromic moderate and severe hearing loss in Pakistan

Abstract

Mutations of GJB2 which encode connexin 26, contribute to 6-7 % of profound deafness in Pakistan. We investigated the involvement of GJB2 mutations in a cohort of 84 pedigrees and 86 sporadic individuals with moderate or severe hearing loss. Individuals in eight consanguineous families and four sporadic cases (9.52 and 4.65 %, respectively) were homozygous or compound heterozygous for p.W24X or p.W77X mutations in GJB2. These two variants are also among the most common mutations known to cause profound deafness in South Asia. The association of identical mutations with both profound and less severe phenotype of hearing loss suggests that alleles of other genes modify the phenotype due to these GJB2 nonsense mutations. Our study demonstrates that GJB2 mutations are an important contributor to aetiology of moderate to severe hearing loss in Pakistan.

Figure 1. Pedigrees of four families in which the affected individuals exhibit intrafamilial differences in hearing thresholds

Black circle’s and squares represent affected female and male participants, respectively. The double horizontal lines denote consanguineous marriages. The genotype for the mutation in GJB2 is provided below each symbol representing the participant. The audiograms on the right side of each pedigree represent the hearing thresholds of the left and the right ears of the affected individuals, respectively.