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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...

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Autores principales: Yano, Takuya, Nishio, Shin-ya, Usami, Shin-ichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
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.
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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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