SLC26A4 Pathogenic Variants as a Third Cause of Hearing Loss: Role of Three Exons in DFNB4 Deafness in Iran.

Context: Pathogenic variants in SLC26A4 gene are the third-most frequent cause of autosomal recessive hearing loss in different populations. Aims: This article reports results of homozygosity mapping and SLC26A4 variant analysis in Iran. Settings and Design: A case series study was performed on forty GJB2-negative Iranian deaf families. Subjects and Methods: Homozygosity mapping, using microsatellite markers flanking the SLC26A4 gene, was performed on GJB2-negative Iranian deaf families. The SLC26A4 variant analysis was done by Sanger sequencing. A literature review was performed to identify all reported SLC26A4 pathogenic variants in Iran. Results: In one of the families, the hearing loss showed co-segregation with the DFNB4 STR markers. A previously reported SLC26A4 pathogenic variant was identified in homozygous state in all the affected members of this family. The literature review showed that variant screening of only three SLC26A4 exons and their boundary regions can detect variants responsible for deafness in about half of all DFNB4 Iranian deaf cases. Conclusions: The results of this study emphasize the important role of SLC26A4 pathogenic variants in the development of deafness in Iran. More information on the frequency of pathogenic variants can help in choosing faster and cost-effective methods for genetic testing. [ABSTRACT FROM AUTHOR]