Whole-Exome Sequencing Identifies a Recurrent Small In-Frame Deletion in MYO15A Causing Autosomal Recessive Nonsyndromic Hearing Loss in 3 Iranian Pedigrees

Abstract

Abstract Background Hearing loss (HL) is the most prevalent and genetically heterogeneous sensory disabilities in humans throughout the world. Methods In this study, we used whole-exome sequencing (WES) to determine the variant causing autosomal recessive nonsyndromic hearing loss (ARNSHL) segregating in 3 separate Iranian consanguineous families (with 3 different ethnicities: Azeri, Persian, and Lur), followed by cosegregation analysis, computational analysis, and structural modeling using the I-TASSER (Iterative Threading ASSEmbly Refinement) server. Also, we used speech-perception tests to measure cochlear implant (CI) performance in patients. Results One small in-frame deletion variant (MYO15A c.8309_8311del (p.Glu2770del)), resulting in deletion of a single amino-acid residue was identified. We found it to be cosegregating with the disease in the studied families. We provide some evidence suggesting the pathogenesis of this variant in HL based on the American College of Medical Genetics (ACMG) and Genomics guidelines. Evaluation of auditory and speech performance indicated favorable outcome after cochlear implantation in our patients. Conclusions The findings of this study demonstrate the utility of WES in genetic diagnostics of HL.