Prevalence and clinical features of autosomal dominant and recessive TMC1-associated hearing loss

Shin-Ya Nishio,Shin-Ichi Usami

doi:10.1007/s00439-021-02364-2

Shin-Ya Nishio, Shin-Ichi Usami

Open Access

https://doi.org/10.1007/s00439-021-02364-2

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Journal: Human Genetics	Publication Date: Sep 14, 2021
Citations: 7	License type: open-access

Affiliation: Shinshu University

Abstract

TMC1 is a causative gene for both autosomal dominant non-syndromic hearing loss (DFNA36) and autosomal recessive non-syndromic hearing loss (DFNB7/11). To date, 125 pathogenic variants in TMC1 have been reported. Most of the TMC1 variants are responsible for autosomal recessive hearing loss, with only 8 variants reported as causative for DFNA36. Here, we reported the prevalence of TMC1-associated hearing loss in a large non-syndromic hearing loss cohort of about 12,000 subjects. As a result, we identified 26 probands with TMC1-associated hearing loss, with the estimated prevalence of TMC1-associated hearing loss in the Japanese hearing loss cohort being 0.17% among all patients. Among the 26 probands with TMC1-associated hearing loss, 15 cases were identified from autosomal dominant hearing loss families. Based on the audiometric data from the probands, family members and previously reported cases, we evaluated hearing deterioration for DFNA36 patients. In addition, we performed haplotype analysis for 11 unrelated autosomal dominant hearing loss families carrying the same variant TMC1: NM_138691:c.1627G > A:p.Asp543Asn. The results clearly indicated that the same haplotype was present despite the families being unrelated, supporting the contention that this variant occurred by founder mutation.

Highlights

Hearing loss is one of the most common sensory disorders and, currently, approximately 120 genes have been reported as causative for non-syndromic hearing loss (The Hereditary Hearing Loss Homepage)
Most cases of TMC1-associated hearing loss are identified as autosomal recessive inherited hearing loss, and only limited cases are identified as autosomal dominant
The TMC1 gene variants associated with autosomal dominant non-syndromic hearing loss (ADNSHL) are p.Ile266Thr (Sloan-Heggen et al 2016), p.Ser320Arg (Hassan et al 2015), p.Tyr381Asn (Likar et al 2018), p.Gly417Arg (Yang et al 2010), p.Met418Lys (Zhao et al 2014; Wang et al 2018), p.Asp543Asn

Summary

Introduction

Hearing loss is one of the most common sensory disorders and, currently, approximately 120 genes have been reported as causative for non-syndromic hearing loss (The Hereditary Hearing Loss Homepage). TMC1 is a causative gene for both autosomal dominant non-syndromic hearing loss (ADNSHL) and autosomal recessive non-syndromic hearing loss (ARNSHL) as first reported by Kurima et al (2002). TMC1 variants are a relatively common genetic cause of non-syndromic hearing loss, and accounts for 3.4% (19/557) of Pakistani ARNSHL patients (Kitajiri et al 2007a, b), 2.4% (3/125) of Chinese ARNSHL patients (Yang et al 2013), 0.69% (3/433) of Chinese hearing loss patients (Yuan et al 2020), 3.1% (4/131) of Western European GJB2-negative. Most cases of TMC1-associated hearing loss are identified as autosomal recessive inherited hearing loss, and only limited cases are identified as autosomal dominant. TMC1-associated ARNSHL cases show congenital severe-to-profound hearing loss, whereas ADNSHL cases show late-onset progressive hearing loss with predominant deterioration in the higher frequencies. The TMC1 gene variants associated with ADNSHL are p.Ile266Thr (Sloan-Heggen et al 2016), p.Ser320Arg (Hassan et al 2015), p.Tyr381Asn (Likar et al 2018), p.Gly417Arg (Yang et al 2010), p.Met418Lys (Zhao et al 2014; Wang et al 2018), p.Asp543Asn (Moteki et al. Vol.:(0123456789)

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