Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Erythron Pathobiology and Genetics lab, Isfahan, Iran.
Lab Med. 2022 Mar 7;53(2):111-122. doi: 10.1093/labmed/lmab047.
Hearing loss (HL) is the most prevalent and genetically heterogeneous sensory disabilities in humans throughout the world.
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.
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.
The findings of this study demonstrate the utility of WES in genetic diagnostics of HL.
听力损失（HL）是全世界最常见且遗传异质性最强的感觉性残疾。
在这项研究中，我们使用全外显子组测序（WES）来确定在 3 个不同的伊朗近亲家族（具有 3 种不同的种族：阿塞拜疆人、波斯人和卢尔人）中分离的常染色体隐性非综合征性听力损失（ARNSHL）的变异，随后进行共分离分析、计算分析和使用 I-TASSER（迭代线程组装精修）服务器进行结构建模。此外，我们还使用言语感知测试来测量患者的人工耳蜗（CI）性能。
发现了一个小的框内缺失变异（MYO15A c.8309_8311del（p.Glu2770del）），导致单个氨基酸残基缺失。我们发现它与研究家族中的疾病共分离。根据美国医学遗传学学院（ACMG）和基因组学指南，我们提供了一些证据表明该变异在 HL 中的发病机制。对听觉和言语表现的评估表明，我们的患者在接受人工耳蜗植入后取得了良好的效果。
这项研究的结果表明，WES 在 HL 的遗传诊断中具有实用性。
