JBCGenetics |

Background: Sensorineural hearing loss is among the most common sensory defects worldwide. Nonsyndromic hearing loss (NSHL) accounts for 70% of inherited hearing loss. The genetic causes of NSHL are considered heterogeneous. The high rate of consanguineous marriages in Saudi Arabia increases the population's prevalence of autosomal recessive inheritance patterns.

Objective: To discover a novel variant for NSHL patients.

Methods: A family with two hearing-impaired children was recruited. Targeted exome sequencing, the Twist Exome 2.0 kit (Twist Bioscience) using the Novaseq X plus platform, was used to identify the variant. Sanger sequencing was carried out to confirm the finding and perform segregation analysis. MutationTaster tool was used to determine the pathogenicity effect on the protein structure.

Results: A homozygous two-bp duplication variant on the (c.8813_8814dup) MYO15A gene was identified in a Saudi family of two hearing-impaired children. Sanger sequencing confirmed the variant in the affected children and their parents. The prediction tool indicated the frameshift effect on the protein level, which leads to protein function disruption. Based on the American College of Medical Genetics and Genomics guidelines, it is classified as a pathogenic variant.

Conclusion: A novel biallelic frameshift variant in MYO15A causes NSHL in a Saudi family. This variant is considered rare and isolated to the Saudi population. Expanded genotype-phenotype correlations for hearing loss patients are likely to confirm the findings and reveal novel variants.

Keywords: Nonsyndromic hearing loss, MYO15A, novel, frameshift, Saudi.