Department of Genetics and Molecular Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Department of Genetics at Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
BMC Med Genet. 2020 Nov 18;21(1):226. doi: 10.1186/s12881-020-01168-x.
Clinical genetic diagnosis of non-syndromic hearing loss (NSHL) is quite challenging. With regard to its high heterogeneity as well as large size of some genes, it is also really difficult to detect causative mutations using traditional approaches. One of the recent technologies called whole-exome sequencing (WES) has been thus developed in this domain to remove the limitations of conventional methods.
This study was a report on a research study of two unrelated pedigrees with multiple affected cases of hearing loss (HL). Accordingly, clinical evaluations and genetic analysis were performed in both families.
The results of WES data analysis to uncover autosomal recessive non-syndromic hearing loss (ARNSHL) disease-causing variants was reported in the present study. Initial analysis identified two novel variants of MYO15A i.e. c.T6442A:p.W2148R and c.10504dupT:p.C3502Lfs*15 correspondingly which were later confirmed by Sanger validations and segregation analyses. According to online prediction tools, both identified variants seemed to have damaging effects.
In this study, whole exome sequencing were used as a first approach strategy to identify the two novel variants in MYO15A in two Iranian families with ARNSHL.
非综合征型听力损失（NSHL）的临床基因诊断极具挑战性。由于其高度异质性和一些基因较大，使用传统方法检测致病突变也非常困难。因此，该领域开发了一种称为全外显子组测序（WES）的新技术，以消除传统方法的局限性。
本研究报告了对两个具有多个听力损失（HL）受累病例的无关家系的研究。因此，在两个家族中均进行了临床评估和遗传分析。
本研究报告了通过 WES 数据分析揭示常染色体隐性非综合征性听力损失（ARNSHL）致病变异的结果。初步分析鉴定出 MYO15A 的两个新变异体，即 c.T6442A:p.W2148R 和 c.10504dupT:p.C3502Lfs*15，随后通过 Sanger 验证和分离分析进行了确认。根据在线预测工具，这两种鉴定出的变异体似乎都具有破坏性影响。
在这项研究中，我们使用全外显子组测序作为一种策略，首先在两个具有 ARNSHL 的伊朗家系中鉴定出 MYO15A 的两个新变异体。
