We present detailed comparative analyses to assess population-level differences in patterns of genetic deafness between European/American and Japanese cohorts with non-syndromic hearing loss. One thousand eighty-three audiometric test results (921 European/American and 162 Japanese) from members of 168 families (48 European/American and 120 Japanese) with non-syndromic hearing loss secondary to pathogenic variants in one of three genes (KCNQ4, TECTA, WFS1) were studied. Audioprofile characteristics, specific mutation types, and protein domains were considered in the comparative analyses. Our findings support differences in audioprofiles driven by both mutation type (non-truncating vs. truncating) and ethnic background. The former finding confirms data that ascribe a phenotypic consequence to different mutation types in KCNQ4; the latter finding suggests that there are ethnic-specific effects (genetic and/or environmental) that impact gene-specific audioprofiles for TECTA and WFS1. Identifying the drivers of ethnic differences will refine our understanding of phenotype-genotype relationships and the biology of hearing and deafness.

中文翻译：

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欧洲/美国和日本人群遗传性听力损失表型的比较分析。

我们提出了详细的比较分析，以评估欧洲/美国和日本非综合征性听力损失队列之间遗传性耳聋模式的人口水平差异。来自 168 个家庭（48 个欧洲/美国和 120 个日本）的成员的 1083 项听力测试结果（921 个欧洲/美国和 162 个日本）继发于三个基因（KCNQ4、TECTA）之一的致病性变异的非综合征性听力损失, WFS1) 进行了研究。在比较分析中考虑了 Audioprofile 特征、特定突变类型和蛋白质结构域。我们的研究结果支持由突变类型（非截断与截断）和种族背景驱动的音频配置文件的差异。前一个发现证实了将表型结果归因于 KCNQ4 中不同突变类型的数据；后一个发现表明，存在影响 TECTA 和 WFS1 的基因特定音频配置文件的种族特定效应（遗传和/或环境）。确定种族差异的驱动因素将完善我们对表型-基因型关系以及听力和耳聋生物学的理解。