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Novel ACTG1 mutations in patients identified by massively parallel DNA sequencing cause progressive hearing loss
Human ACTG1 mutations are associated with high-frequency hearing loss, and patients with mutations in this gene are good candidates for electric acoustic stimulation. To better understand the genetic etiology of hearing loss cases, massively parallel DNA sequencing was performed on 7,048 unrelated J...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184572/ https://www.ncbi.nlm.nih.gov/pubmed/32341388 http://dx.doi.org/10.1038/s41598-020-63690-5 |
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author | Miyajima, Hiroki Moteki, Hideaki Day, Timothy Nishio, Shin-ya Murata, Takaaki Ikezono, Tetsuo Takeda, Hidehiko Abe, Satoko Iwasaki, Satoshi Takahashi, Masahiro Naito, Yasushi Yamazaki, Hiroshi Kanda, Yukihiko Kitajiri, Shin-ichiro Usami, Shin-ichi |
author_facet | Miyajima, Hiroki Moteki, Hideaki Day, Timothy Nishio, Shin-ya Murata, Takaaki Ikezono, Tetsuo Takeda, Hidehiko Abe, Satoko Iwasaki, Satoshi Takahashi, Masahiro Naito, Yasushi Yamazaki, Hiroshi Kanda, Yukihiko Kitajiri, Shin-ichiro Usami, Shin-ichi |
author_sort | Miyajima, Hiroki |
collection | PubMed |
description | Human ACTG1 mutations are associated with high-frequency hearing loss, and patients with mutations in this gene are good candidates for electric acoustic stimulation. To better understand the genetic etiology of hearing loss cases, massively parallel DNA sequencing was performed on 7,048 unrelated Japanese hearing loss probands. Among 1,336 autosomal dominant hearing loss patients, we identified 15 probands (1.1%) with 13 potentially pathogenic ACTG1 variants. Six variants were novel and seven were previously reported. We collected and analyzed the detailed clinical features of these patients. The average progression rate of hearing deterioration in pure-tone average for four frequencies was 1.7 dB/year from 0 to 50 years age, and all individuals over 60 years of age had severe hearing loss. To better understand the underlying disease-causing mechanism, intracellular localization of wild-type and mutant gamma-actins were examined using the NIH/3T3 fibroblast cell line. ACTG1 mutants p.I34M p.M82I, p.K118M and p.I165V formed small aggregates while p.R37H, p.G48R, p.E241K and p.H275Y mutant gamma-actins were distributed in a similar manner to the WT. From these results, we believe that some part of the pathogenesis of ACTG1 mutations may be driven by the inability of defective gamma-actin to be polymerized into F-actin. |
format | Online Article Text |
id | pubmed-7184572 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-71845722020-04-29 Novel ACTG1 mutations in patients identified by massively parallel DNA sequencing cause progressive hearing loss Miyajima, Hiroki Moteki, Hideaki Day, Timothy Nishio, Shin-ya Murata, Takaaki Ikezono, Tetsuo Takeda, Hidehiko Abe, Satoko Iwasaki, Satoshi Takahashi, Masahiro Naito, Yasushi Yamazaki, Hiroshi Kanda, Yukihiko Kitajiri, Shin-ichiro Usami, Shin-ichi Sci Rep Article Human ACTG1 mutations are associated with high-frequency hearing loss, and patients with mutations in this gene are good candidates for electric acoustic stimulation. To better understand the genetic etiology of hearing loss cases, massively parallel DNA sequencing was performed on 7,048 unrelated Japanese hearing loss probands. Among 1,336 autosomal dominant hearing loss patients, we identified 15 probands (1.1%) with 13 potentially pathogenic ACTG1 variants. Six variants were novel and seven were previously reported. We collected and analyzed the detailed clinical features of these patients. The average progression rate of hearing deterioration in pure-tone average for four frequencies was 1.7 dB/year from 0 to 50 years age, and all individuals over 60 years of age had severe hearing loss. To better understand the underlying disease-causing mechanism, intracellular localization of wild-type and mutant gamma-actins were examined using the NIH/3T3 fibroblast cell line. ACTG1 mutants p.I34M p.M82I, p.K118M and p.I165V formed small aggregates while p.R37H, p.G48R, p.E241K and p.H275Y mutant gamma-actins were distributed in a similar manner to the WT. From these results, we believe that some part of the pathogenesis of ACTG1 mutations may be driven by the inability of defective gamma-actin to be polymerized into F-actin. Nature Publishing Group UK 2020-04-27 /pmc/articles/PMC7184572/ /pubmed/32341388 http://dx.doi.org/10.1038/s41598-020-63690-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Miyajima, Hiroki Moteki, Hideaki Day, Timothy Nishio, Shin-ya Murata, Takaaki Ikezono, Tetsuo Takeda, Hidehiko Abe, Satoko Iwasaki, Satoshi Takahashi, Masahiro Naito, Yasushi Yamazaki, Hiroshi Kanda, Yukihiko Kitajiri, Shin-ichiro Usami, Shin-ichi Novel ACTG1 mutations in patients identified by massively parallel DNA sequencing cause progressive hearing loss |
title | Novel ACTG1 mutations in patients identified by massively parallel DNA sequencing cause progressive hearing loss |
title_full | Novel ACTG1 mutations in patients identified by massively parallel DNA sequencing cause progressive hearing loss |
title_fullStr | Novel ACTG1 mutations in patients identified by massively parallel DNA sequencing cause progressive hearing loss |
title_full_unstemmed | Novel ACTG1 mutations in patients identified by massively parallel DNA sequencing cause progressive hearing loss |
title_short | Novel ACTG1 mutations in patients identified by massively parallel DNA sequencing cause progressive hearing loss |
title_sort | novel actg1 mutations in patients identified by massively parallel dna sequencing cause progressive hearing loss |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184572/ https://www.ncbi.nlm.nih.gov/pubmed/32341388 http://dx.doi.org/10.1038/s41598-020-63690-5 |
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