BACKGROUND Hearing loss (HL) represents the most common congenital sensory impairment with an incidence of 1-5 per 1000 live births. Non-syndromic hearing loss (NSHL) is an isolated finding that is not part of any other disorder accounting for 70% of all genetic hearing loss cases. METHODS In the current study, we reported a polygenic mode of inheritance in an NSHL consanguineous family using exome sequencing technology and we evaluated the possible effect of the detected single nucleotide variants (SNVs) using in silico methods. RESULTS Two bi-allelic SNVs were detected in the affected patients; a MYO15A (. p.V485A) variant, and a novel MITF (p.P338L) variant. Along with these homozygous mutations, we detected two heterozygous variants in well described hearing loss genes (MYO7A and MYH14). The novel MITF p. Pro338Leu missense mutation was predicted to change the protein structure and function. CONCLUSION A novel MITF mutation along with a previously described MYO15A mutation segregate with an autosomal recessive non-syndromic HL case with a post-lingual onset. The findings highlight the importance of carrying whole exome sequencing for a comprehensive assessment of HL genetic heterogeneity.

中文翻译：

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舌后非综合征性听力损失表型：MYO15A和MITF中有2个双等位基因突变的多基因病例。

背景技术听力损失（HL）代表最常见的先天性感觉障碍，每1000例活产中有1-5例。非综合征性听力损失（NSHL）是一个孤立的发现，不属于任何其他疾病的一部分，占所有遗传性听力损失病例的70％。方法在当前研究中，我们报告了使用外显子组测序技术在NSHL血缘家族中的多基因遗传模式，并使用计算机方法评估了检测到的单核苷酸变体（SNV）的可能作用。结果在患病患者中检测到两个双等位SNV。MYO15A（.p.V485A）变体和新型MITF（p.P338L）变体。除这些纯合突变外，我们在描述良好的听力损失基因（MYO7A和MYH14）中检测到两个杂合变异。小说MITF p。Pro338Leu错义突变预计会改变蛋白质的结构和功能。结论新型MITF突变与先前描述的MYO15A突变与常染色体隐性非综合征性HL病例分离，并伴有舌后发作。这些发现突出了进行完整的外显子组测序对HL遗传异质性的全面评估的重要性。