Whole exome sequencing identifies novel compound heterozygous pathogenic variants in the MYO15A gene leading to autosomal recessive non-syndromic hearing loss
Autor: | Hamidreza Abtahi, Akram Sarmadi, Sina Narrei, Zahra Nouri, Mohammad Amin Tabatabaiefar, Samane Nasrniya |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Proband Adult Male MYO15A medicine.medical_specialty Hearing loss Genomics Genes Recessive Biology Deafness Iran Myosins Compound heterozygosity 03 medical and health sciences symbols.namesake 0302 clinical medicine Exome Sequencing otorhinolaryngologic diseases Genetics medicine Humans Exome Child Hearing Loss Molecular Biology Exome sequencing Sanger sequencing General Medicine Pedigree 030104 developmental biology 030220 oncology & carcinogenesis Mutation symbols Medical genetics Female medicine.symptom |
Zdroj: | Molecular biology reports. 47(7) |
ISSN: | 1573-4978 |
Popis: | 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. |
Databáze: | OpenAIRE |
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