Molecular Otolaryngology and Renal Research Labs, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.
Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto, Nagano, 390-8621, Japan.
Hum Genet. 2020 Oct;139(10):1315-1323. doi: 10.1007/s00439-020-02174-y. Epub 2020 May 7.
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.
我们进行了详细的对比分析，以评估欧洲/美国和日本人群中非综合征性听力损失的遗传耳聋模式的人群水平差异。从三个基因（KCNQ4、TECTA、WFS1）中的一个致病性变异导致的非综合征性听力损失的 168 个家庭（48 个欧洲/美国和 120 个日本）的 168 名成员中，研究了 1083 项听力测试结果（921 个欧洲/美国和 162 个日本）。在对比分析中考虑了听力学特征、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（非截断型与截断型）和种族背景引起的听力学特征差异。这一发现证实了归因于 KCNQ4 中不同突变类型的表型后果的数据；后一发现表明，存在影响 TECTA 和 WFS1 基因特异性听力特征的种族特异性影响（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-基因型关系和听力与耳聋生物学的理解。
