Autosomal recessive non-syndromic hearing loss (ARNSHL) is the most common form of hearing loss with the involvement of at least 50 genes. Genetic linkage analysis (GLA) is a powerful strategy for study of genetic disease. On the other hand, the next-generation sequencing (NGS) is revolutionizing the genetic diagnostics. Here we applied a combined GLA and NGS strategy to elucidate the genetic etiology of ARNSHL in Khuzestan province of Iran. Materials and methods Totally, 25 multiplex consanguineous ARNSHL families were recruited from Khuzestan province of Iran. GJB2 mutations were investigated using Sanger sequencing. A panel of 10 loci was selected for GLA followed by Sanger sequencing. Several families negative for the studied genes were sequenced by NGS using Otogenetics deafness panel which included 129 genes. Results Four families had GJB2 mutations. GLA revealed 2 families linked to DFNB4, 1 to DFNB2, 2 to DFNB7/11 and 1 to DFNB9. Two families subject to NGS showed causative variants in two rare genes. Conclusion Totally, 5 loci accounted for 40% of deafness etiology. Given the large genes of DFNB2 and DFNB9, as a diagnostic algorithm, after exclusion of GJB2, SLC26A4 and TMC1 mutations, the remaining families could be subject to NGS. Furthermore, Iran NGS panel (s) could be developed to enable deafness diagnostics at very low cost focusing on very small fraction of the genome while leading to a rather high diagnostic yield.
