Four Novel Variants in POU4F3 Cause Autosomal Dominant Nonsyndromic Hearing Loss
Four Novel Variants in POU4F3 Cause Autosomal Dominant Nonsyndromic Hearing Loss
复制标题
POU4F3 的四种新变体导致常染色体显性非综合征性听力损失。
DOI：
10.1155/2020/6137083
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发表时间：
2020-07-01
影响因子：
3.1
通讯作者：
Yuan, Yong-Yi
中科院分区：
文献类型：
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作者：
Cui, Tian-Yi;Gao, Xue;Yuan, Yong-Yi
遗传性耳聋是世界范围内最常见的感觉性障碍之一。POU结构域4转录因子3(POU4F3)突变被认为是常染色体显性遗传性非综合征性耳聋(ADNSHL)的致病因素。本研究通过定向下一代测序和Sanger测序，在4个不同的ADNSHL家系中发现了POU4F3、c.696G和gt；T(p.Glu232Asp)、c.325C和gt；T(p.His109Tyr)、c.635T和gt；C(p.Leu212Pro)和c.183delG(p.Ala62Argfs*22)四个新的突变。根据美国医学遗传学和基因组学指南，c.183delG(p.Ala62Argfs*22)被归类为致病变异，c.696G>；T(p.Glu232Asp)和c.635T>；C(p.Leu212Pro)被归类为可能的致病变异，c.325C>；T(p.His109Tyr)被归类为意义不确定的变异。根据以往的报道和本研究的结果，我们推测POU4F3致病变异体是东亚人群ADNSHL的重要致病因素。因此，筛查POU4F3应作为遗传性耳聋诊断的常规检查。
Hereditary hearing loss is one of the most common sensory disabilities worldwide. Mutation of POU domain class 4 transcription factor 3(POU4F3) is considered the pathogenic cause of autosomal dominant nonsyndromic hearing loss (ADNSHL), designated as autosomal dominant nonsyndromic deafness 15. In this study, four novel variants in POU4F3, c.696G>T (p.Glu232Asp), c.325C>T (p.His109Tyr), c.635T>C (p.Leu212Pro), and c.183delG (p.Ala62Argfs*22), were identified in four different Chinese families with ADNSHL by targeted next-generation sequencing and Sanger sequencing. Based on the American College of Medical Genetics and Genomics guidelines, c.183delG (p.Ala62Argfs*22) is classified as a pathogenic variant, c.696G>T (p.Glu232Asp) and c.635T>C (p.Leu212Pro) are classified as likely pathogenic variants, and c.325C>T (p.His109Tyr) is classified as a variant of uncertain significance. Based on previous reports and the results of this study, we speculated that POU4F3 pathogenic variants are significant contributors to ADNSHL in the East Asian population. Therefore, screening of POU4F3 should be a routine examination for the diagnosis of hereditary hearing loss.