Comprehensive molecular-genetic analysis of mid-frequency sensorineural hearing loss

Abstract The genetic heterogeneity of sensorineural hearing loss (SNHL) is a major hurdle to the detection of disease-causing variants. We aimed to identify underlying causal genes associated with mid-frequency hearing loss (HL), which contributes to less than about 1% of SNHL cases, by whole exome...

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Autores principales:	Zuzana Pavlenkova, Lukas Varga, Silvia Borecka, Miloslav Karhanek, Miloslava Huckova, Martina Skopkova, Milan Profant, Daniela Gasperikova
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d07c4be76fda4d4d81919144ffb8c089
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spelling	oai:doaj.org-article:d07c4be76fda4d4d81919144ffb8c0892021-11-21T12:19:05ZComprehensive molecular-genetic analysis of mid-frequency sensorineural hearing loss10.1038/s41598-021-01876-12045-2322https://doaj.org/article/d07c4be76fda4d4d81919144ffb8c0892021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01876-1https://doaj.org/toc/2045-2322Abstract The genetic heterogeneity of sensorineural hearing loss (SNHL) is a major hurdle to the detection of disease-causing variants. We aimed to identify underlying causal genes associated with mid-frequency hearing loss (HL), which contributes to less than about 1% of SNHL cases, by whole exome sequencing (WES). Thirty families segregating mid-frequency SNHL, in whom biallelic GJB2 mutations had been previously excluded, were selected from among 851 families in our DNA repository of SNHL. DNA samples from the probands were subjected to WES analysis and searched for candidate variants associated with SNHL. We were able to identify the genetic aetiology in six probands (20%). In total, we found three pathogenic and three likely pathogenic variants in four genes (COL4A5, OTOGL, TECTA, TMPRSS3). One more proband was a compound heterozygote for a pathogenic variant and a variant of uncertain significance (VUS) in MYO15A gene. To date, MYO15A and TMPRSS3 have not yet been described in association with mid-frequency SNHL. In eight additional probands, eight candidate VUS variants were detected in five genes (DIAPH1, MYO7A, TECTA, TMC1, TSPEAR). Seven of these 16 variants have not yet been published or mentioned in the available databases. The most prevalent gene was TECTA, identified in 23% of all tested families. Furthermore, we confirmed the hypothesis that a substantive portion of cases with this conspicuous audiogram shape is a consequence of a genetic disorder.Zuzana PavlenkovaLukas VargaSilvia BoreckaMiloslav KarhanekMiloslava HuckovaMartina SkopkovaMilan ProfantDaniela GasperikovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zuzana Pavlenkova Lukas Varga Silvia Borecka Miloslav Karhanek Miloslava Huckova Martina Skopkova Milan Profant Daniela Gasperikova Comprehensive molecular-genetic analysis of mid-frequency sensorineural hearing loss
description	Abstract The genetic heterogeneity of sensorineural hearing loss (SNHL) is a major hurdle to the detection of disease-causing variants. We aimed to identify underlying causal genes associated with mid-frequency hearing loss (HL), which contributes to less than about 1% of SNHL cases, by whole exome sequencing (WES). Thirty families segregating mid-frequency SNHL, in whom biallelic GJB2 mutations had been previously excluded, were selected from among 851 families in our DNA repository of SNHL. DNA samples from the probands were subjected to WES analysis and searched for candidate variants associated with SNHL. We were able to identify the genetic aetiology in six probands (20%). In total, we found three pathogenic and three likely pathogenic variants in four genes (COL4A5, OTOGL, TECTA, TMPRSS3). One more proband was a compound heterozygote for a pathogenic variant and a variant of uncertain significance (VUS) in MYO15A gene. To date, MYO15A and TMPRSS3 have not yet been described in association with mid-frequency SNHL. In eight additional probands, eight candidate VUS variants were detected in five genes (DIAPH1, MYO7A, TECTA, TMC1, TSPEAR). Seven of these 16 variants have not yet been published or mentioned in the available databases. The most prevalent gene was TECTA, identified in 23% of all tested families. Furthermore, we confirmed the hypothesis that a substantive portion of cases with this conspicuous audiogram shape is a consequence of a genetic disorder.
format	article
author	Zuzana Pavlenkova Lukas Varga Silvia Borecka Miloslav Karhanek Miloslava Huckova Martina Skopkova Milan Profant Daniela Gasperikova
author_facet	Zuzana Pavlenkova Lukas Varga Silvia Borecka Miloslav Karhanek Miloslava Huckova Martina Skopkova Milan Profant Daniela Gasperikova
author_sort	Zuzana Pavlenkova
title	Comprehensive molecular-genetic analysis of mid-frequency sensorineural hearing loss
title_short	Comprehensive molecular-genetic analysis of mid-frequency sensorineural hearing loss
title_full	Comprehensive molecular-genetic analysis of mid-frequency sensorineural hearing loss
title_fullStr	Comprehensive molecular-genetic analysis of mid-frequency sensorineural hearing loss
title_full_unstemmed	Comprehensive molecular-genetic analysis of mid-frequency sensorineural hearing loss
title_sort	comprehensive molecular-genetic analysis of mid-frequency sensorineural hearing loss
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d07c4be76fda4d4d81919144ffb8c089
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Comprehensive molecular-genetic analysis of mid-frequency sensorineural hearing loss

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