RESUMO
Mutations in the SLC26A4 gene in the DFNB4 locus is responsible for syndromic [Pendred syndrome] and non-syndromic hereditary hearing loss [HHL]. In many populations, mutations in this gene have been reported as a second cause of HHL. The objective of this study was to investigate the prevalence of SLC26A4 mutations in our HHL consanguineous families. After completing clinical evaluation and obtaining signed consent forms from each family, we included 80 families with two or more affected individuals, referred to the Genetics Research Center [GRC]. All families that previously tested negative for the DFNB1 locus were candidates for homozygosity mapping using STRs for DFNB4 locus. Families localized to this region were subjected to complete DMA sequencing. Twelve out of 80 families were mapped to DFNB4. Sequence analysis of 12 linked families revealed 10 mutations in 8 families. [T420I, 1197delT, G334V, R409H, T721M, R79X, S448L, L597S, 965insA, and L445W]. The T420I, G334V, L597S and R79X were novel mutations; we did not find any mutation in the four linked families, nor did we detect any nonsyndromic families with mutation in the SLC26A4 gene. We have been able to identify mutation in the SLC26A4 gene in only 8 of 80 families. In 12 families, we detected some degree of diffuse or nodular goiter; three out of 12 families showed thyroid function impairment and in five of 12 families there were positive prechlorate discharge tests. Eight families that showed mutation had normal temporal bone scan. This investigation, demonstrated that the SLC26A4 gene mutation is the most prevalent syndromic hereditary hearing loss in Iran, a finding in accordance with reports from other countries