Whole exome sequencing identifies novel compound heterozygous pathogenic variants in the MYO15A gene leading to autosomal recessive non-syndromic hearing loss

被引：0
作者：
Akram Sarmadi
Samane Nasrniya
Sina Narrei
Zahra Nouri
Hamidreza Abtahi
Mohammad Amin Tabatabaiefar
机构：
[1] Isfahan University of Medical Sciences,Department of Genetics and Molecular Biology, School of Medicine
[2] Erythron Pathobiology and Genetics lab,Genetics Department
[3] Isfahan University of Medical Sciences,Department of Otolaryngology, Al
[4] Isfahan University of Medical Sciences,Zahra Hospital
[5] Isfahan University of Medical Sciences,Pediatric Inherited Diseases Research Center, Research Institute for Primordial Prevention of Noncommunicable Disease
来源：
Molecular Biology Reports | 2020年 / 47卷
关键词：
Compound heterozygous; Hearing loss; Whole exome sequencing; Iran; Pathogenic variant;
D O I：
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学科分类号：
摘要：
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.
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页码：5355 / 5364
页数：9
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