Supplementary Material for: The p.R206C Mutation in <b><i>MYO7A</i></b> Leads to Autosomal Dominant Nonsyndromic Hearing Loss

<b><i>Background:</i></b> Dominant mutations in <i>MYO7A</i> may lead to nonsyndromic deafness DFNA11. A p.R206C variant in <i>MYO7A</i> has previously been reported in a small deaf family from Taiwan but with ambiguous pathogenicity and inheritance pattern. <b><i>Aims/Objectives:</i></b> Our study aims to clarify the pathogenicity of this variant by clinical characterization and genetic analysis of a separate autosomal dominant deaf family harboring this variant in mainland China. <b><i>Materials and Methods:</i></b> Auditory features of hearing loss were characterized in representative affected family members. Mutation screening was performed by targeted next-generation sequencing of 138 known deafness genes in the proband. Candidate pathogenic mutations were confirmed by Sanger sequencing in family members and ethnically matched controls. <b><i>Results:</i></b> Consistent with typical DFNA11 phenotype, the affected family members in this study showed delayed-onset, progressive hearing loss affecting mostly high frequencies. Targeted next-generation sequencing identified a p.R206C mutation in <i>MYO7A</i> as the only candidate pathogenic mutation cosegregating with the hearing phenotype. This mutation is not seen in 200 Chinese Han normal-hearing controls. <b><i>Conclusions and Significance:</i></b> The recurrent p.R206C variant in <i>MYO7A</i> is pathogenic and is likely in a mutation hot spot or due to a founder effect. Reports of such rare variants in multiple patients or families may facilitate exploitation of its pathogenicity.

**背景：** MYO7A基因的显性突变可导致非综合征性耳聋DFNA11。MYO7A基因的p.R206C变异此前曾在台湾的一个小型耳聋家族中被报道，但该变异的致病性与遗传模式尚不明确。
**研究目的：** 本研究旨在通过对中国大陆另一个携带该变异的常染色体显性遗传性耳聋家族进行临床表型分析与遗传学检测，明确该变异的致病性。
**材料与方法：** 对代表性受累家族成员的听力损失听觉特征进行分析。本研究对先证者的138个已知耳聋基因进行靶向下一代测序（targeted next-generation sequencing）以完成突变筛查，并通过桑格测序（Sanger sequencing）对家族成员及种族匹配对照人群中的候选致病突变进行验证。
**结果：** 本研究中的受累家族成员表现出以高频听力受损为主的迟发性、进行性听力损失，与典型DFNA11表型一致。靶向下一代测序检测发现，MYO7A基因的p.R206C突变是唯一与听力表型共分离的候选致病突变。在200名中国汉族正常听力对照人群中未检测到该突变。
**结论与意义：** MYO7A基因的p.R206C复发性变异具有致病性，该变异可能位于突变热点区域，或源于奠基者效应。在多个患者或家族中报道此类罕见变异，有助于进一步阐明其致病机制。

搜集汇总

背景与挑战

背景概述

该数据集是《MYO7A基因中p.R206C突变导致常染色体显性非综合征性听力损失》研究的补充材料，包含临床和遗传分析数据，用于支持该突变的致病性结论。数据集通过靶向下一代测序和Sanger测序方法，在中国汉族常染色体显性耳聋家族中验证了p.R206C突变与进行性高频听力损失的表型共分离，且未在正常听力对照组中发现，强调了该变异在DFNA11听力损失中的致病作用。