Frequency of GJB2 mutations in families with autosomal recessive non-syndromic hearing loss in Khuzestan province

Abstract

Hearing loss is caused both by genetic and environmental factors. In this sense, more than half of the cases are genetic. Hereditary hearing loss is divided into syndromic and non-syndromic cases. Main pattern of inheritance (80%) in non-syndromic cases is autosomal recessive, which is known as autosomal recessive non-syndromic hearing loss (ARNSHL). Although the disease is very genetically heterogeneous, the GJB2 gene has highest effect. The aim of the present research is to determine the role of GJB2 mutations and DFNB1 locus in a group of families with ARNSHL in Khuzestan province of Iran. This study was conducted on 50 large families with ARNSHL (with the priority of 4 patients) in Khuzestan province, southwest Iran. First, in order to study GJB2 gene mutations, direct sequencing was conducted in all families. Besides, in the families with negative or heterozygous mutations in GJB2, linkage analysis was done using STR (Short Tandem Repeat) markers related to DFNB1 locus. Genotypes, related to each family, were determined using PCR-PAGE method. From 50 families with ARNSHL, after direct sequencing, six families (12%) showed homozygote mutations in the GJB2 gene. Accordingly, it was observed that c.35delG was the most frequent mutation (50%) in the population. Moreover, c.358-360delGAG, c.506G>A, c.71G>A mutations were identified in 3 different families. In addition, no linkage was observed in DFNB1 locus for the remaining families. Low frequency (12%) of GJB2 mutations in our study suggests that other loci and genes should be addressed to elucidate the etiology of ARNSHL in this province.