A comparative analysis of genetic hearing loss phenotypes in European/American and Japanese populations
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ORIGINAL INVESTIGATION
A comparative analysis of genetic hearing loss phenotypes in European/American and Japanese populations W. Daniel Walls1 · Hideaki Moteki2 · Taylor R. Thomas1 · Shin‑ya Nishio2 · Hidekane Yoshimura2 · Yoichiro Iwasa2 · Kathy L. Frees1 · Carla J. Nishimura1 · Hela Azaiez1 · Kevin T. Booth1,3 · Robert J. Marini1 · Diana L. Kolbe1 · A. Monique Weaver1 · Amanda M. Schaefer1 · Kai Wang4 · Terry A. Braun5 · Shin‑ichi Usami2 · Peter G. Barr‑Gillespie6 · Guy P. Richardson7 · Richard J. Smith1,10,11 · Thomas L. Casavant5,8,9 Received: 25 October 2019 / Accepted: 29 April 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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 genespecific 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.
Introduction Hearing loss is the most common sensory defect, affecting roughly 466 million people worldwide (World Health Organization 2019). Its prevalence in newborns is 1.7 per Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00439-020-02174-y) contains supplementary material, which is available to authorized users. * Richard J. Smith richard‑[email protected] 1
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
1000 births (Centers for Disease Control and Prevention 2018) but climbs dramatically to affect 50% of octogenarians (Fortnum et al. 2001; Morton and Nance 2006). Causality is broadly considered to be genetic and/or environmental, with the majority of congenital hearing loss in developed countries being genetic (Korver et al. 2017). Adult-onset hearing loss is considerably more complex and reflects the impact
6
Vollum Institute, Oregon Health & Science University, Portland, OR 97239, USA
7
Sussex Neuroscience, School of Life Sciences, University of Sussex, Brighton, UK
8
Center for Bioinformatics and Computational Biology, Uni
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