Genetic analysis of TRIOBP and MYO15A variants in Iranian families with autosomal recessive non-syndromic hearing loss

Deafness is a prevalent sensory and neurological disorder that impacts over 466 million individuals globally. Congenital deafness is the most prevalent birth defect, occurring in approximately 2–3 out of every 1000 births. It is recognized as a highly diverse condition. >50% of congenital deafness has genetic causes and the rest is due to environmental causes or both. With the development of next-generation sequencing and bioinformatics tools, whole-exome sequencing has been proposed as one of the effective methods for diagnosing genetics of hearing loss. Five Iranian Autosomal recessive non-syndromic hearing loss (ARNSHL) families negative for GJB2 (NM_004004.6) gene mutations from Sistan and Baluchestan province were selected for further study by whole-exome sequencing analysis. The analysis procedure was performed using multiple bioinformatics tools and websites after filling the consent form and extracting DNA from whole blood using the salting out method. After detecting the variants in priority and confirming them in the probands by Sanger sequencing, other family members were studied to confirm the variant within the family. After analyzing the families recruited for this study, four known genes along with known and novel variants were discovered. Mutations found in the MYO15A, SLC26A4, TRIOBP and TECTA genes among which, the variants found in TRIOBP (NM_001039141.3, p.R283X) and MYO15A (NM_016239.4, p.P2880Rfs*19) were novel. Other known variants were TECTA (NM_005422.4, p.W1534X) and SLC26A4 (NM_000441.2, p.V239D). No genes or variants that might contribute to hearing loss have been identified within one of the families. Our study's findings support previous research that has identified SLC26A4, MYO15A, and TECTA genes as common genetic factors following GJB2 in our population. •Whole Exome Sequencing detected variations in MYO15A, SLC26A4, TRIOBP, and TECTA within Iranian families with autosomal recessive non-syndromic hearing loss.•Novel mutations were found in TRIOBP (p.R283X) and MYO15A (p.P2880Rfs*19) that had not been reported before.•All affected patients were homozygous for the mutant variant.•The variants co-segregated with the disease in the families.