Hearing loss (HL) is the most common sensorineural disorder with high phenotypic and genotypic heterogeneity, which negatively affects life quality. Autosomal recessive non-syndromic hearing loss (ARNSHL) constitutes a major share of HL cases. In the present study, Whole exome sequencing (WES) was applied to investigate the underlying etiology of HL in an Iranian patient with ARNSHL. A proband from an Iranian consanguineous family was examined via WES, following GJB2 sequencing. WES was utilized to find possible genetic etiology of the disease. Various Bioinformatics tools were used to assess the pathogenicity of the variants. Co-segregation analysis of the candidate variant was carried out. Interpretation of variants was performed according to the American College of Medical Genetics and Genomics (ACMG) guidelines. WES results showed a novel frameshift (16 bp deletion) variant (p.Ala170Alafs*20) in the LRTOMT gene. This variant, which resides in exon 6, was found to be co-segregating in the family. It fulfils the criteria set by the ACMG guidelines of being pathogenic. Here, we report successful application of WES to identify the molecular pathogenesis of ARNSHL, which is a genetically heterogeneous disorder, in a patient with ARNSHL.

中文翻译：

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LRTOMT基因中的一种新型致病变体导致伊朗家庭中的常染色体隐性非综合征性听力损失。

听力损失（HL）是最常见的感觉神经疾病，具有高表型和基因型异质性，对生活质量产生负面影响。常染色体隐性隐性非综合征性听力损失（ARNSHL）构成HL病例的主要部分。在本研究中，全外显子组测序（WES）用于研究伊朗ARNSHL患者的HL的潜在病因。在进行GJB2测序后，通过WES检查了来自伊朗近亲家庭的先证者。WES被用于寻找该疾病的可能遗传病因。各种生物信息学工具被用来评估变异的致病性。进行了候选变体的共分离分析。根据美国医学遗传学和基因组学学院（ACMG）指南对变体进行解释。WES结果显示LRTOMT基因中有一个新的移码（16 bp缺失）变异（p.Ala170Alafs * 20）。该变体位于外显子6，被发现在该家族中共同分离。它符合ACMG致病性准则设定的标准。在这里，我们报道了WES在ARNSHL患者中成功应用WES鉴定ARNSHL的分子发病机理的原因，ARNSHL是一种遗传异质性疾病。