Screening of GJB2 (35delG, W24X, W77X) and GJB6 (D13S1830) Mutations in Patients with Non-syndromic Hereditary Hearing Impairment

Abstract

Hereditary hearing impairment affects approximately 1 in 1000 children worldwide. In most populations, the main causative agent is GJB2 gene (MIM#121011) located at chromosome 13q12.11 which encodes for a gap junction protein called connexin 26. Mutations in gap junction proteins, GJB2 and GJB6, another protein residing near the former with similar function, affect the K+ concentration in the hair cells of cochlea, a major functional player within inner ear. In this study, we screened three already reported GJB2 mutations (35delG, W24X, W77X) and a reported GJB6 mutation (delD13S1830) in a group of Pakistani individuals suffering from congenital non-syndromic, severe to profound hearing impairment through PCR using mutation specific and normal primers. In 43 out of 77 patients tested, one of three GJB2 mutations was present (55.83%). Out of these, W24X was found to be the most frequent (27/77), accounting for 35.06% of the studied sample, while frequency of W27X was 10/77 (12.98%) and of 35delG 6/77 (7.79%). No samples were reported carrying the GJB6 deletion encompassing microsatellite marker D13S1830. There are mixed reports about the prevalence of GJB2 mutations in Pakistan which may be due to the different in ethnicities of the highly diverse Pakistani population. This suggests the important role of ancestry in disease heterogeneity.