Introduction & Objective : Hearing loss is the most prevalent form of sensory impairment in humans, affecting approximately one in 1000 infants. In more than half of the cases, the deafness is inherited, and about 80% of hereditary deafness transmitted by autosomal recessive pattern. In hereditary congenital deafness, numerous mutations in GJB2 make the largest fractional contribution in many world populations. The GJB2 gene locus was identified in long arm of chromosome 13 (13q11-12).

Materials & Methods : In this study, we investigated 76 probands (152 chromosomes) of 76 families from Hamadan Province, suffering from severe to profound non-syndromic deafness, to determine the frequencies of GJB2 mutations. All samples were screened for 35delG mutation in GJB2 gene by allele-specific PCR (ARMS-PCR). Study was terminated for those who were homozygote for 35delG mutation. DHPLC analysis had been done on others to find abnormal elution profiles, followed by direct sequencing on samples with abnormal elution profiles.             

Results : We identified allelic variants and mutations in exons 1 & 2 of CX26 ( 35delG, R127H, V27I, V153I, E114G, -3170G>A). Interestingly we found a novel frame-shift mutation (507insAACG), that was not reported before in related medical literature. Also we detected a previously reported complex allelic variant "V27IE114G/wt. 11 persons carried the 35delG allele (8 homozygote, 3 heterozygote), 2 cases were compound heterozygote for 35delG/wt and 3170G>A/wt and 1 proband showed the V27IE114G/wt mutation.

Conclusion : Based on these data, GJB2 mutations account for approximately 18.1% of severe-to-profound congenital deafness in the Hamadan population, and the most common of this mutation is 35delG.