Mutation screening of GJB2 and GJB6 and genetic linkage study of three prevalent DFNB loci in Iranian families with autosomal recessive non-syndromic hearing loss

The incidence of prelingual hearing loss (HL) is about 1 in 1000 neonates of which, more than 60% of cases are inherited. Non-syndromic HL (NSHL) is extremely heterogeneous: more than 100 loci have been identified. The most common form of NSHL is the autosomal recessive form (ARNSHL). Here, we have investigated CX26 (GJB2) and CX30 (GJB6) gene mutation and linkage analysis of 3 known loci in Iranian families. A cohort of 36 big ARNSHL pedigrees from 7 provinces of Iran was investigated. All of the families were examined for the presence of GJB2 and GJB6 (del D13S1830 and del D13S1854) mutations using direct sequencing and multiplex PCR, respectively. The negative mutations pedigrees for the above- mentioned mutations, were then tested for the linkage to the 3 known loci, including DFNB3(MYO7A), DFNB4(SLC26A4) and DFNB7/11(TMC1), using STR markers and conventional PCR and PAGE. Six families had GJB2 mutations. No GJB6 mutation was found. Totally, 3 families showed linkage to DFNB4 and 1 family was linked to DFNB7/11. DFNB1 (GJB2) and DFNB4 are the main causes of ARNSHL in our study samples and GJB6 mutations are apparently absent in the Iranian population