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Identification of four TMC1 variations in different Chinese families with hereditary hearing loss
BACKGROUND: 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 fa...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081220/ https://www.ncbi.nlm.nih.gov/pubmed/29654653 http://dx.doi.org/10.1002/mgg3.394 |
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author | Wang, Hongyang Wu, Kaiwen Guan, Jing Yang, Ju Xie, Linyi Xiong, Fen Lan, Lan Wang, Dayong Wang, Qiuju |
author_facet | Wang, Hongyang Wu, Kaiwen Guan, Jing Yang, Ju Xie, Linyi Xiong, Fen Lan, Lan Wang, Dayong Wang, Qiuju |
author_sort | Wang, Hongyang |
collection | PubMed |
description | BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. |
format | Online Article Text |
id | pubmed-6081220 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60812202018-08-09 Identification of four TMC1 variations in different Chinese families with hereditary hearing loss Wang, Hongyang Wu, Kaiwen Guan, Jing Yang, Ju Xie, Linyi Xiong, Fen Lan, Lan Wang, Dayong Wang, Qiuju Mol Genet Genomic Med Original Articles BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. John Wiley and Sons Inc. 2018-04-14 /pmc/articles/PMC6081220/ /pubmed/29654653 http://dx.doi.org/10.1002/mgg3.394 Text en © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Wang, Hongyang Wu, Kaiwen Guan, Jing Yang, Ju Xie, Linyi Xiong, Fen Lan, Lan Wang, Dayong Wang, Qiuju Identification of four TMC1 variations in different Chinese families with hereditary hearing loss |
title | Identification of four TMC1 variations in different Chinese families with hereditary hearing loss |
title_full | Identification of four TMC1 variations in different Chinese families with hereditary hearing loss |
title_fullStr | Identification of four TMC1 variations in different Chinese families with hereditary hearing loss |
title_full_unstemmed | Identification of four TMC1 variations in different Chinese families with hereditary hearing loss |
title_short | Identification of four TMC1 variations in different Chinese families with hereditary hearing loss |
title_sort | identification of four tmc1 variations in different chinese families with hereditary hearing loss |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081220/ https://www.ncbi.nlm.nih.gov/pubmed/29654653 http://dx.doi.org/10.1002/mgg3.394 |
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