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Whole Exome Sequencing Identifies Novel Compound Heterozygous Pathogenic Variants in the Myo15a Gene Leading to Autosomal Recessive Non-Syndromic Hearing Loss Publisher Pubmed



Sarmadi A1, 2 ; Nasrniya S1 ; Narrei S2 ; Nouri Z2 ; Abtahi H3 ; Tabatabaiefar MA1, 4, 5
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. Genetics Department, 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, 81746-73461, Iran
  5. 5. GenTArget Corp (GTAC), Deputy of Research and Technology, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Molecular Biology Reports Published:2020


Abstract

Autosomal recessive non-syndromic hearing loss (ARNSHL) is a highly heterogeneous disease, for which more than 70 genes have been identified. MYO15A mutations have been reported to cause congenital severe-to-profound HL. In this study, we applied the whole exome sequencing (WES) to find the cause of HL in an Iranian family. A proband from an Iranian non-consanguineous family with hearing impaired parents, was examined via WES, after excluding GJB2 mutations as the most common ARNSHL gene via Sanger sequencing. Co-segregation analysis of the candidate variant was done in the family members. Interpretation of variants was according to the American College of Medical Genetics and Genomics (ACMG) guidelines. WES results showed novel compound heterozygous variants (p.Arg1507Ter and p.Val2815Valfs*10) in the MYO15A gene. These two variants, residing in highly conserved regions, were found to be co-segregating in the family and fulfill the criteria of being categorized as pathogenic, according to the ACMG guidelines. Here, we report successful application of WES to identify the molecular pathogenesis of ARNSHL in a patient with ARNSHL, as an example of an extremely heterogeneous disease. In agreement with previous studies, MYO15A is regarded to be important in causing HL in Iran. © 2020, Springer Nature B.V.
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