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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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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. |
format | Online Article Text |
id | pubmed-7678220 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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