Mutation analysis of GJB2 and GJB6 genes and screening of nine common dfnb loci in iranian pedigrees with autosomal recessive nonsyndromic hearing loss

Background: Hearing loss (HL) is one of the most common sensory disorders (1/1000). Various studies have shown that a large proportion of autosomal recessive nonsyndromic HL (ARNSHL) in Iranian populations is caused by defects in a certain number of genes; new detection methods such as sequencing of the exome (exome-sequencing) can increase the frequency identification of responsible mutations for HL. The aim of this study was to screen for ARNSHL pedigrees and to find the responsible genes. Materials and Methods: Fifty big ARNSHL pedigrees including 130 Iranian patients with ARNSHL took part in this study. Direct sequencing and multiplex polymerase chain reaction were, respectively, used for the presence of GJB2 and GJB6 (del D13S1830 and del D13S1854) mutations in all of the families. The negative pedigrees for these genes were tested to homozygosity mapping for the linkage to nine known loci, then the negative pedigrees for them were sent for exome-sequencing. Results: Nine of 50 pedigrees had GJB2 ( 18%) mutations. No GJB6 mutation was found. Totally, 11 of 50 pedigrees (22%) showed linkage to 6 known loci DFNB, including 2 pedigrees to DFNB2, 2 pedigrees to DFNB3, 2 pedigrees to DFNB4, 2 pedigrees to DFNB7/11, 3 pedigrees to DFNB12, and 2 pedigrees to DFNB104. An individual from a large pedigree was examined by exome-sequencing and was observed no changes. Conclusion: In this study, DFNB1 and DFNB12 are the main causes of ARNSHL. GJB6 mutations, DFNB6, and DFNB59 were absent. Therefore, 40% of the ARNSHL etiology was found in this study