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Screening for mitochondrial 12S rRNA C1494T mutation in 655 patients with non-syndromic hearing loss: An observational study

Mutations in mitochondrial DNA, especially in 12S rRNA gene, are the most important causes for hearing loss. In particular, the A1555G and C1494T mutations have been found to be associated with both aminoglycoside-induced and non-syndromic hearing loss in many families worldwide. To determine the fr...

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Autores principales: Gao, Zhen, Yuan, Ya-Sheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220552/
https://www.ncbi.nlm.nih.gov/pubmed/32221064
http://dx.doi.org/10.1097/MD.0000000000019373
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author Gao, Zhen
Yuan, Ya-Sheng
author_facet Gao, Zhen
Yuan, Ya-Sheng
author_sort Gao, Zhen
collection PubMed
description Mutations in mitochondrial DNA, especially in 12S rRNA gene, are the most important causes for hearing loss. In particular, the A1555G and C1494T mutations have been found to be associated with both aminoglycoside-induced and non-syndromic hearing loss in many families worldwide. To determine the frequency of C1494T mutation in deaf patients, in the current study, we screened this mutation in 655 patients with non-syndromic hearing loss and 300 control subjects. After PCR amplification of mitochondrial 12S rRNA gene and direct sequence analysis, we found that there were 2 patients carrying the C1494T mutation; however, this mutation was not detected in 300 healthy subjects. Further genetic counseling suggested that only 1 patient had an obvious family history of hearing impairment. Clinical evaluation showed that 3 of 10 matrilineal relatives suffered from hearing loss, with different age at onset of hearing loss. Molecular analysis revealed the presence of homoplasmic 12S rRNA C1494T and ND5 T12338C mutations, together with a set of polymorphisms belonging to human mitochondrial haplogroup F2. Interestingly, T12338C mutation resulted in the replacement of the first amino acid, a translation-initiating methionine with a threonine, shortening 2 amino acids of ND5 polypeptide. Moreover, this mutation is located in 2 nucleotides adjacent to the 3’ end of the mt-tRNALeu(CUN) gene. Therefore, this mutation may alter ND5 mRNA metabolism and the processing of RNA precursors. Thus, the combination of T12338C and C1494T mutations may contribute to deafness expression in this family. Taken together, our data suggested that the C1494T mutation was the molecular basis for hearing loss, screening for the mitochondrial DNA pathogenic mutations was recommended for early detection, prevention, and diagnosis of mitochondrial deafness.
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spelling pubmed-72205522020-06-15 Screening for mitochondrial 12S rRNA C1494T mutation in 655 patients with non-syndromic hearing loss: An observational study Gao, Zhen Yuan, Ya-Sheng Medicine (Baltimore) 6000 Mutations in mitochondrial DNA, especially in 12S rRNA gene, are the most important causes for hearing loss. In particular, the A1555G and C1494T mutations have been found to be associated with both aminoglycoside-induced and non-syndromic hearing loss in many families worldwide. To determine the frequency of C1494T mutation in deaf patients, in the current study, we screened this mutation in 655 patients with non-syndromic hearing loss and 300 control subjects. After PCR amplification of mitochondrial 12S rRNA gene and direct sequence analysis, we found that there were 2 patients carrying the C1494T mutation; however, this mutation was not detected in 300 healthy subjects. Further genetic counseling suggested that only 1 patient had an obvious family history of hearing impairment. Clinical evaluation showed that 3 of 10 matrilineal relatives suffered from hearing loss, with different age at onset of hearing loss. Molecular analysis revealed the presence of homoplasmic 12S rRNA C1494T and ND5 T12338C mutations, together with a set of polymorphisms belonging to human mitochondrial haplogroup F2. Interestingly, T12338C mutation resulted in the replacement of the first amino acid, a translation-initiating methionine with a threonine, shortening 2 amino acids of ND5 polypeptide. Moreover, this mutation is located in 2 nucleotides adjacent to the 3’ end of the mt-tRNALeu(CUN) gene. Therefore, this mutation may alter ND5 mRNA metabolism and the processing of RNA precursors. Thus, the combination of T12338C and C1494T mutations may contribute to deafness expression in this family. Taken together, our data suggested that the C1494T mutation was the molecular basis for hearing loss, screening for the mitochondrial DNA pathogenic mutations was recommended for early detection, prevention, and diagnosis of mitochondrial deafness. Wolters Kluwer Health 2020-03-27 /pmc/articles/PMC7220552/ /pubmed/32221064 http://dx.doi.org/10.1097/MD.0000000000019373 Text en Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc. http://creativecommons.org/licenses/by-nc/4.0 This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0
spellingShingle 6000
Gao, Zhen
Yuan, Ya-Sheng
Screening for mitochondrial 12S rRNA C1494T mutation in 655 patients with non-syndromic hearing loss: An observational study
title Screening for mitochondrial 12S rRNA C1494T mutation in 655 patients with non-syndromic hearing loss: An observational study
title_full Screening for mitochondrial 12S rRNA C1494T mutation in 655 patients with non-syndromic hearing loss: An observational study
title_fullStr Screening for mitochondrial 12S rRNA C1494T mutation in 655 patients with non-syndromic hearing loss: An observational study
title_full_unstemmed Screening for mitochondrial 12S rRNA C1494T mutation in 655 patients with non-syndromic hearing loss: An observational study
title_short Screening for mitochondrial 12S rRNA C1494T mutation in 655 patients with non-syndromic hearing loss: An observational study
title_sort screening for mitochondrial 12s rrna c1494t mutation in 655 patients with non-syndromic hearing loss: an observational study
topic 6000
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220552/
https://www.ncbi.nlm.nih.gov/pubmed/32221064
http://dx.doi.org/10.1097/MD.0000000000019373
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