The clinical and genetic spectrum of twenty-six individuals with hearing loss affected by MYO15A variants

Abstract

Abstract Myosin XVA (MYO15A) is a member of the myosin superfamily that, as a motor protein, plays an essential role in actin polymerization at the tip of the stereocilia in hair cells. Variants in MYO15A are known to be the third most common reason for autosomal recessive non-syndromic hearing loss (ARNSHL). Here, we present twenty-six unrelated families with MYO15A variants from an Iranian cohort. Whole exome sequencing (WES) was performed following a comprehensive medical evaluation. The identified variants were assessed based on the American College of Medical Genetics and Genomics guidelines. Twenty-seven distinct variants linked to MYO15A were identified as contributors to profound ARNSHL. These included ten novel variants and seventeen previously documented variants that co-segregated. Most variants were truncating, with an equal distribution of missense and splicing variants. This research expands the mutational spectrum of MYO15A by introducing ten novel variants and highlights its importance in profound ARNSHL. Moreover, comparing the variants in different domains of MYO15A with previously reported variants in these domains provides more information about the MYO15A protein’s role in the hearing process. This information can enhance understanding of the genetic basis of hearing loss and improve future management strategies, including prognosis, prevention, and treatment based on gene modification.

Keywords

• Hearing loss
• DFNB3
• MYO15A
• Domain
• Whole-exome sequencing
• Hair cell