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.
