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The Analysis of A Frequent TMPRSS3 Allele Containing P.V116M and P.V291L in A Cis Configuration among Deaf Koreans

We performed targeted re-sequencing to identify the genetic etiology of early-onset postlingual deafness and encountered a frequent TMPRSS3 allele harboring two variants in a cis configuration. We aimed to evaluate the pathogenicity of the allele. Among 88 cochlear implantees with autosomal recessiv...

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Autores principales: Kim, Ah Reum, Chung, Juyong, Kim, Nayoung K. D., Lee, Chung, Park, Woong-Yang, Oh, Doo-Yi, Choi, Byung Yoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713216/
https://www.ncbi.nlm.nih.gov/pubmed/29072634
http://dx.doi.org/10.3390/ijms18112246
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author Kim, Ah Reum
Chung, Juyong
Kim, Nayoung K. D.
Lee, Chung
Park, Woong-Yang
Oh, Doo-Yi
Choi, Byung Yoon
author_facet Kim, Ah Reum
Chung, Juyong
Kim, Nayoung K. D.
Lee, Chung
Park, Woong-Yang
Oh, Doo-Yi
Choi, Byung Yoon
author_sort Kim, Ah Reum
collection PubMed
description We performed targeted re-sequencing to identify the genetic etiology of early-onset postlingual deafness and encountered a frequent TMPRSS3 allele harboring two variants in a cis configuration. We aimed to evaluate the pathogenicity of the allele. Among 88 cochlear implantees with autosomal recessive non-syndromic hearing loss, subjects with GJB2 and SLC26A4 mutations were excluded. Thirty-one probands manifesting early-onset postlingual deafness were sorted. Through targeted re-sequencing, we detected two families with a TMPRSS3 mutant allele containing p.V116M and p.V291L in a cis configuration, p.[p.V116M; p.V291L]. A minor allele frequency was calculated and proteolytic activity was measured. A p.[p.V116M; p.V291L] allele demonstrated a significantly higher frequency compared to normal controls and merited attention due to its high frequency (4.84%, 3/62). The first family showed a novel deleterious splice site variant—c.783-1G>A—in a trans allele, while the other showed homozygosity. The progression to deafness was noted within the first decade, suggesting DFNB10. The proteolytic activity was significantly reduced, confirming the severe pathogenicity. This frequent mutant allele significantly contributes to early-onset postlingual deafness in Koreans. For clinical implication and proper auditory rehabilitation, it is important to pay attention to this allele with a severe pathogenic potential.
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spelling pubmed-57132162017-12-07 The Analysis of A Frequent TMPRSS3 Allele Containing P.V116M and P.V291L in A Cis Configuration among Deaf Koreans Kim, Ah Reum Chung, Juyong Kim, Nayoung K. D. Lee, Chung Park, Woong-Yang Oh, Doo-Yi Choi, Byung Yoon Int J Mol Sci Article We performed targeted re-sequencing to identify the genetic etiology of early-onset postlingual deafness and encountered a frequent TMPRSS3 allele harboring two variants in a cis configuration. We aimed to evaluate the pathogenicity of the allele. Among 88 cochlear implantees with autosomal recessive non-syndromic hearing loss, subjects with GJB2 and SLC26A4 mutations were excluded. Thirty-one probands manifesting early-onset postlingual deafness were sorted. Through targeted re-sequencing, we detected two families with a TMPRSS3 mutant allele containing p.V116M and p.V291L in a cis configuration, p.[p.V116M; p.V291L]. A minor allele frequency was calculated and proteolytic activity was measured. A p.[p.V116M; p.V291L] allele demonstrated a significantly higher frequency compared to normal controls and merited attention due to its high frequency (4.84%, 3/62). The first family showed a novel deleterious splice site variant—c.783-1G>A—in a trans allele, while the other showed homozygosity. The progression to deafness was noted within the first decade, suggesting DFNB10. The proteolytic activity was significantly reduced, confirming the severe pathogenicity. This frequent mutant allele significantly contributes to early-onset postlingual deafness in Koreans. For clinical implication and proper auditory rehabilitation, it is important to pay attention to this allele with a severe pathogenic potential. MDPI 2017-10-26 /pmc/articles/PMC5713216/ /pubmed/29072634 http://dx.doi.org/10.3390/ijms18112246 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Ah Reum
Chung, Juyong
Kim, Nayoung K. D.
Lee, Chung
Park, Woong-Yang
Oh, Doo-Yi
Choi, Byung Yoon
The Analysis of A Frequent TMPRSS3 Allele Containing P.V116M and P.V291L in A Cis Configuration among Deaf Koreans
title The Analysis of A Frequent TMPRSS3 Allele Containing P.V116M and P.V291L in A Cis Configuration among Deaf Koreans
title_full The Analysis of A Frequent TMPRSS3 Allele Containing P.V116M and P.V291L in A Cis Configuration among Deaf Koreans
title_fullStr The Analysis of A Frequent TMPRSS3 Allele Containing P.V116M and P.V291L in A Cis Configuration among Deaf Koreans
title_full_unstemmed The Analysis of A Frequent TMPRSS3 Allele Containing P.V116M and P.V291L in A Cis Configuration among Deaf Koreans
title_short The Analysis of A Frequent TMPRSS3 Allele Containing P.V116M and P.V291L in A Cis Configuration among Deaf Koreans
title_sort analysis of a frequent tmprss3 allele containing p.v116m and p.v291l in a cis configuration among deaf koreans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713216/
https://www.ncbi.nlm.nih.gov/pubmed/29072634
http://dx.doi.org/10.3390/ijms18112246
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