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Frequency of mitochondrial mutations in non-syndromic hearing loss as well as possibly responsible variants found by whole mitochondrial genome screening
Mutations in mitochondrial DNA (mtDNA) are reported to be responsible for the pathogenesis of maternally inherited hearing loss. Complete mtDNA sequencing may detect pathogenic mutations, but whether they are indeed pathogenic can be difficult to interpret because of normal ethnic-associated haplogr...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970901/ https://www.ncbi.nlm.nih.gov/pubmed/24401907 http://dx.doi.org/10.1038/jhg.2013.128 |
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author | Yano, Takuya Nishio, Shin-ya Usami, Shin-ichi |
author_facet | Yano, Takuya Nishio, Shin-ya Usami, Shin-ichi |
author_sort | Yano, Takuya |
collection | PubMed |
description | Mutations in mitochondrial DNA (mtDNA) are reported to be responsible for the pathogenesis of maternally inherited hearing loss. Complete mtDNA sequencing may detect pathogenic mutations, but whether they are indeed pathogenic can be difficult to interpret because of normal ethnic-associated haplogroup variation and other rare variations existing among control populations. In this study, we performed systemic mutational analysis of mtDNA in 394 Japanese patients with hearing loss. Two different cohorts were analyzed in this study: Cohort 1, 254 maternally inherited patients; and Cohort 2, 140 patients with various inheritance modes. After screening of the entire mtDNA genome with direct sequencing, we evaluated the frequency of previously reported mutations and the frequency and pathogenicity of the novel variants. As a result, the ‘Confirmed' mitochondrial mutations were found predominantly in Cohort 1 rather than in Cohort 2 (14.6 vs 0.7%). 1555A>G (n=23) is the most common mutation, followed by the 3243A>G (n=11) mutations. On the basis of prediction analysis, we detected 10 novel homoplasmic mitochondrial variants. After further classification, the 3595A>G and 6204A>G variants were found to be new candidate mutations possibly associated with hearing loss. |
format | Online Article Text |
id | pubmed-3970901 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-39709012014-04-01 Frequency of mitochondrial mutations in non-syndromic hearing loss as well as possibly responsible variants found by whole mitochondrial genome screening Yano, Takuya Nishio, Shin-ya Usami, Shin-ichi J Hum Genet Original Article Mutations in mitochondrial DNA (mtDNA) are reported to be responsible for the pathogenesis of maternally inherited hearing loss. Complete mtDNA sequencing may detect pathogenic mutations, but whether they are indeed pathogenic can be difficult to interpret because of normal ethnic-associated haplogroup variation and other rare variations existing among control populations. In this study, we performed systemic mutational analysis of mtDNA in 394 Japanese patients with hearing loss. Two different cohorts were analyzed in this study: Cohort 1, 254 maternally inherited patients; and Cohort 2, 140 patients with various inheritance modes. After screening of the entire mtDNA genome with direct sequencing, we evaluated the frequency of previously reported mutations and the frequency and pathogenicity of the novel variants. As a result, the ‘Confirmed' mitochondrial mutations were found predominantly in Cohort 1 rather than in Cohort 2 (14.6 vs 0.7%). 1555A>G (n=23) is the most common mutation, followed by the 3243A>G (n=11) mutations. On the basis of prediction analysis, we detected 10 novel homoplasmic mitochondrial variants. After further classification, the 3595A>G and 6204A>G variants were found to be new candidate mutations possibly associated with hearing loss. Nature Publishing Group 2014-02 2014-01-09 /pmc/articles/PMC3970901/ /pubmed/24401907 http://dx.doi.org/10.1038/jhg.2013.128 Text en Copyright © 2014 The Japan Society of Human Genetics http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
spellingShingle | Original Article Yano, Takuya Nishio, Shin-ya Usami, Shin-ichi Frequency of mitochondrial mutations in non-syndromic hearing loss as well as possibly responsible variants found by whole mitochondrial genome screening |
title | Frequency of mitochondrial mutations in non-syndromic hearing loss as well as possibly responsible variants found by whole mitochondrial genome screening |
title_full | Frequency of mitochondrial mutations in non-syndromic hearing loss as well as possibly responsible variants found by whole mitochondrial genome screening |
title_fullStr | Frequency of mitochondrial mutations in non-syndromic hearing loss as well as possibly responsible variants found by whole mitochondrial genome screening |
title_full_unstemmed | Frequency of mitochondrial mutations in non-syndromic hearing loss as well as possibly responsible variants found by whole mitochondrial genome screening |
title_short | Frequency of mitochondrial mutations in non-syndromic hearing loss as well as possibly responsible variants found by whole mitochondrial genome screening |
title_sort | frequency of mitochondrial mutations in non-syndromic hearing loss as well as possibly responsible variants found by whole mitochondrial genome screening |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970901/ https://www.ncbi.nlm.nih.gov/pubmed/24401907 http://dx.doi.org/10.1038/jhg.2013.128 |
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