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Characterization of an N-terminal Na(v)1.5 channel variant – a potential risk factor for arrhythmias and sudden death?

BACKGROUND: Alterations in the SCN5A gene encoding the cardiac sodium channel Na(v)1.5 have been linked to a number of arrhythmia syndromes and diseases including long-QT syndrome (LQTS), Brugada syndrome (BrS) and dilative cardiomyopathy (DCM), which may predispose to fatal arrhythmias and sudden d...

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Autores principales: Scheiper-Welling, Stefanie, Zuccolini, Paolo, Rauh, Oliver, Beckmann, Britt-Maria, Geisen, Christof, Moroni, Anna, Thiel, Gerhard, Kauferstein, Silke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678220/
https://www.ncbi.nlm.nih.gov/pubmed/33213388
http://dx.doi.org/10.1186/s12881-020-01170-3
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author Scheiper-Welling, Stefanie
Zuccolini, Paolo
Rauh, Oliver
Beckmann, Britt-Maria
Geisen, Christof
Moroni, Anna
Thiel, Gerhard
Kauferstein, Silke
author_facet Scheiper-Welling, Stefanie
Zuccolini, Paolo
Rauh, Oliver
Beckmann, Britt-Maria
Geisen, Christof
Moroni, Anna
Thiel, Gerhard
Kauferstein, Silke
author_sort Scheiper-Welling, Stefanie
collection PubMed
description BACKGROUND: Alterations in the SCN5A gene encoding the cardiac sodium channel Na(v)1.5 have been linked to a number of arrhythmia syndromes and diseases including long-QT syndrome (LQTS), Brugada syndrome (BrS) and dilative cardiomyopathy (DCM), which may predispose to fatal arrhythmias and sudden death. We identified the heterozygous variant c.316A > G, p.(Ser106Gly) in a 35-year-old patient with survived cardiac arrest. In the present study, we aimed to investigate the functional impact of the variant to clarify the medical relevance. METHODS: Mutant as well as wild type GFP tagged Na(v)1.5 channels were expressed in HEK293 cells. We performed functional characterization experiments using patch-clamp technique. RESULTS: Electrophysiological measurements indicated, that the detected missense variant alters Nav1.5 channel functionality leading to a gain-of-function effect. Cells expressing S106G channels show an increase in Na(v)1.5 current over the entire voltage window. CONCLUSION: The results support the assumption that the detected sequence aberration alters Na(v)1.5 channel function and may predispose to cardiac arrhythmias and sudden cardiac death. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12881-020-01170-3.
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spelling pubmed-76782202020-11-20 Characterization of an N-terminal Na(v)1.5 channel variant – a potential risk factor for arrhythmias and sudden death? Scheiper-Welling, Stefanie Zuccolini, Paolo Rauh, Oliver Beckmann, Britt-Maria Geisen, Christof Moroni, Anna Thiel, Gerhard Kauferstein, Silke BMC Med Genet Research Article BACKGROUND: Alterations in the SCN5A gene encoding the cardiac sodium channel Na(v)1.5 have been linked to a number of arrhythmia syndromes and diseases including long-QT syndrome (LQTS), Brugada syndrome (BrS) and dilative cardiomyopathy (DCM), which may predispose to fatal arrhythmias and sudden death. We identified the heterozygous variant c.316A > G, p.(Ser106Gly) in a 35-year-old patient with survived cardiac arrest. In the present study, we aimed to investigate the functional impact of the variant to clarify the medical relevance. METHODS: Mutant as well as wild type GFP tagged Na(v)1.5 channels were expressed in HEK293 cells. We performed functional characterization experiments using patch-clamp technique. RESULTS: Electrophysiological measurements indicated, that the detected missense variant alters Nav1.5 channel functionality leading to a gain-of-function effect. Cells expressing S106G channels show an increase in Na(v)1.5 current over the entire voltage window. CONCLUSION: The results support the assumption that the detected sequence aberration alters Na(v)1.5 channel function and may predispose to cardiac arrhythmias and sudden cardiac death. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12881-020-01170-3. BioMed Central 2020-11-19 /pmc/articles/PMC7678220/ /pubmed/33213388 http://dx.doi.org/10.1186/s12881-020-01170-3 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Scheiper-Welling, Stefanie
Zuccolini, Paolo
Rauh, Oliver
Beckmann, Britt-Maria
Geisen, Christof
Moroni, Anna
Thiel, Gerhard
Kauferstein, Silke
Characterization of an N-terminal Na(v)1.5 channel variant – a potential risk factor for arrhythmias and sudden death?
title Characterization of an N-terminal Na(v)1.5 channel variant – a potential risk factor for arrhythmias and sudden death?
title_full Characterization of an N-terminal Na(v)1.5 channel variant – a potential risk factor for arrhythmias and sudden death?
title_fullStr Characterization of an N-terminal Na(v)1.5 channel variant – a potential risk factor for arrhythmias and sudden death?
title_full_unstemmed Characterization of an N-terminal Na(v)1.5 channel variant – a potential risk factor for arrhythmias and sudden death?
title_short Characterization of an N-terminal Na(v)1.5 channel variant – a potential risk factor for arrhythmias and sudden death?
title_sort characterization of an n-terminal na(v)1.5 channel variant – a potential risk factor for arrhythmias and sudden death?
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678220/
https://www.ncbi.nlm.nih.gov/pubmed/33213388
http://dx.doi.org/10.1186/s12881-020-01170-3
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