A novel variant of SLC26A4 and first report of the c.716T>A variant in Iranian pedigrees with non-syndromic sensorineural hearing loss

Abstract The autosomal recessive non-syndromic hearing loss (ARNSHL) can be associated with variants in solute carrier family 26, member 4 ( SLC26A4 ) gene and is the second most common cause of ARNSHL worldwide. Therefore, this study aims to determine the contribution of the SLC26A4 genotype in the hearing loss (HL) of 40 ARNSHL pedigrees in Iran. A cohort of the 40 Iranian pedigrees with ARNSHL, having no mutation in the GJB2 gene, was selected. The linkage analysis with five short tandem repeat (STR) markers linked to SLC26A4 was performed for the 40 ARNSHL pedigrees. Then, two out of the 40 pedigrees with ARNSHL that linked to DFNB4 locus were further screened to determine the variants in all exons of SLC26A4 gene by direct DNA sequencing. The 21 exons of SCL26A4 were analyzed for the two pedigrees. A known variant (c.716T>A homozygote), it is the first reported incidence in Iran, a novel variant (c.493A>C homozygote) were detected in the two pedigrees and pathogenesis of c.493A>C confirmed in this study with review 100 hearing ethnically matched controls by PCR-RFLP analysis. The present study suggests that the SLC26A4 gene plays a crucial role in the HL occurring in Iranian pedigrees. Also, the results probably support the specificity and unique spectrum of SLC26A4 variants among Iranian HL patients. Molecular study of SLC26A4 gene may lead to elucidation of the profile of the population-specific variants which has importance in diagnostics of HL.