Dataset Information

Molecular etiology study of hearing loss in 13 Chinese Han families.

ABSTRACT: Hearing loss affecting about 2/1000 newborns is the most common congenital disease. Genetic defects caused approximately 70% of patients who have non-syndromic hearing loss. We recruited 13 Chinese Han deafness families who tested negative for GJB2, SLC26A4, and mitochondrial 12S rRNA. The probands of each family were performed whole-exome sequencing (WES) or targeted next-generation sequencing (NGS) for known deafness genes to study for pathogenic causes. We found four novel mutations of CDH23, one novel mutation of MYO15A, one novel mutation of TMC1, one novel mutation of PAX3, and one novel mutation of ADGRV1, one novel CNV of ADGRV1, and one novel CNV of STRC. Hearing loss is a highly hereditary and heterogeneous disease. The results in the limited samples of this study show that Usher and Waardenburg syndrome-related genes account for a major proportion are strongly associated with Chinese Han hearing loss patients negative for GJB2, SLC26A4, and mitochondrial 12S rRNA, followed by STRC resulting in mild to moderate deafness.

SUBMITTER: Sun L

PROVIDER: S-EPMC9728030 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Molecular etiology study of hearing loss in 13 Chinese Han families.

Sun Lianhua L Lin Zhengyu Z Wang Xiaowen X Shen Jiali J Li Yue Y Huang Yuyu Y Yang Jun J

Frontiers in neurology 20221123

Hearing loss affecting about 2/1000 newborns is the most common congenital disease. Genetic defects caused approximately 70% of patients who have non-syndromic hearing loss. We recruited 13 Chinese Han deafness families who tested negative for <i>GJB2, SLC26A4</i>, and mitochondrial 12S rRNA. The probands of each family were performed whole-exome sequencing (WES) or targeted next-generation sequencing (NGS) for known deafness genes to study for pathogenic causes. We found four novel mutations of ...[more]

PMID: 36504663

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Project description:Variants in TMC1 (transmembrane channel-like 1) can cause both autosomal dominant and recessive hearing loss in human population. Mice with Tmc1 variants have been shown to be ideal animal models for gene therapy. In this article, we report four TMC1 variants in four different Chinese families and the follow-up auditory phenotype of a previously reported family. Four families with TMC1 variants, as well as a previously described family with TMC1 variant orthologous to the Beethoven mouse, were recruited in this study. A comprehensive auditory evaluation was performed on all ascertained family members. High-throughput sequencing was conducted using genomic DNA from the probands and other family members to identify probable deafness genes. We identified four TMC1 (NM_138691.2) variations, including two pathogenic variants, c.1714G>A, and c.1253T>A, one likely pathogenic variant, c.[797T>C];[797T>C], and one single nucleotide polymorphism (SNP), c.2276G>A. Among these variants, c.[797T>C];[797T>C] is a novel likely pathogenic variant, and c.1714G>A and c.1253T>A are known pathogenic variants at the DFNB7/11 (DFNA36) locus. Phenotype-genotype correlation analysis of TMC1 variants showed that the TMC1 dominant variation-related phenotype was late-onset, progressive, high frequency to all frequency sensorineural hearing loss, while the TMC1 recessive variant was related to congenital all frequency sensorineural hearing impairment. Two pathogenic, one likely pathogenic variants and one SNP of TMC1 were identified in four Chinese families with hereditary hearing loss, indicating that TMC1 may be a more frequent cause of hearing loss than expected. TMC1 variants related to hearing loss result in specific phenotypes. The TMC1 c.1253T>A (p.M418K) variation, homologous to the Tmc1 c. 1235 T> A (p.M412K) variant in Beethoven mice, was the second report of this variant in human patients with hearing loss, suggesting the possibility to translational gene therapy from Beethoven mice to human patients.

Dataset Information

Molecular etiology study of hearing loss in 13 Chinese Han families.

Publications

Molecular etiology study of hearing loss in 13 Chinese Han families.

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