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

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.