1. A comparative analysis of genetic hearing loss phenotypes in European/American and Japanese populations.
- Author
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Walls WD, Moteki H, Thomas TR, Nishio SY, Yoshimura H, Iwasa Y, Frees KL, Nishimura CJ, Azaiez H, Booth KT, Marini RJ, Kolbe DL, Weaver AM, Schaefer AM, Wang K, Braun TA, Usami SI, Barr-Gillespie PG, Richardson GP, Smith RJ, and Casavant TL
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Asian People, Audiometry, Case-Control Studies, Child, Child, Preschool, Female, GPI-Linked Proteins genetics, Gene Expression, Genetic Association Studies, Hearing Loss, Sensorineural diagnosis, Hearing Loss, Sensorineural ethnology, Hearing Loss, Sensorineural physiopathology, Humans, Infant, Infant, Newborn, Japan, Male, Middle Aged, Pedigree, Phenotype, United States, White People, Extracellular Matrix Proteins genetics, Genotype, Hearing Loss, Sensorineural genetics, KCNQ Potassium Channels genetics, Membrane Proteins genetics, Mutation
- 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 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.
- Published
- 2020
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