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Whole-Exome Sequencing Identifies a Recurrent Small In-Frame Deletion in Myo15a Causing Autosomal Recessive Nonsyndromic Hearing Loss in 3 Iranian Pedigrees Publisher Pubmed



Nasrniya S1 ; Miar P1 ; Narrei S2 ; Sepehrnejad M6 ; Nilforoush MH6 ; Abtahi H3, 5 ; Tabatabaiefar MA1, 2, 4
Authors
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Authors Affiliations
  1. 1. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Erythron Pathobiology and Genetics lab, Isfahan, Iran
  3. 3. Department of Otolaryngology, Al-Zahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
  5. 5. Department of Ear, Nose & Throat, and Head & Neck Surgery, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  6. 6. Department of Audiology, School of Rehabilitation Sciences, Isfahan University of Medical Sciences University of Medical Sciences, Isfahan, Iran

Source: Lab Medicine Published:2022


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. © American Society for Clinical Pathology, 2021. All rights reserved.
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