Disease Modifiers of Inherited SCN5A Channelopathy
To date, a large number of mutations in SCN5A, the gene encoding the pore-forming α-subunit of the primary cardiac Na+ channel (NaV1.5), have been found in patients presenting with a wide range of ECG abnormalities and cardiac syndromes. Although these mutations all affect the same NaV1.5 channel, t...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2018-10-01
|
Series: | Frontiers in Cardiovascular Medicine |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fcvm.2018.00137/full |
id |
doaj-67d16f4fadbf4c5991e83ad9a738252c |
---|---|
record_format |
Article |
spelling |
doaj-67d16f4fadbf4c5991e83ad9a738252c2020-11-25T00:26:46ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2018-10-01510.3389/fcvm.2018.00137409341Disease Modifiers of Inherited SCN5A ChannelopathyArie O. Verkerk0Arie O. Verkerk1Ahmad S. Amin2Carol Ann Remme3Department of Clinical and Experimental Cardiology, Heart Centre, Academic Medical Center, Amsterdam, NetherlandsDepartment of Medical Biology, Academic Medical Center, Amsterdam, NetherlandsDepartment of Clinical and Experimental Cardiology, Heart Centre, Academic Medical Center, Amsterdam, NetherlandsDepartment of Clinical and Experimental Cardiology, Heart Centre, Academic Medical Center, Amsterdam, NetherlandsTo date, a large number of mutations in SCN5A, the gene encoding the pore-forming α-subunit of the primary cardiac Na+ channel (NaV1.5), have been found in patients presenting with a wide range of ECG abnormalities and cardiac syndromes. Although these mutations all affect the same NaV1.5 channel, the associated cardiac syndromes each display distinct phenotypical and biophysical characteristics. Variable disease expressivity has also been reported, where one particular mutation in SCN5A may lead to either one particular symptom, a range of various clinical signs, or no symptoms at all, even within one single family. Additionally, disease severity may vary considerably between patients carrying the same mutation. The exact reasons are unknown, but evidence is increasing that various cardiac and non-cardiac conditions can influence the expressivity and severity of inherited SCN5A channelopathies. In this review, we provide a summary of identified disease entities caused by SCN5A mutations, and give an overview of co-morbidities and other (non)-genetic factors which may modify SCN5A channelopathies. A comprehensive knowledge of these modulatory factors is not only essential for a complete understanding of the diverse clinical phenotypes associated with SCN5A mutations, but also for successful development of effective risk stratification and (alternative) treatment paradigms.https://www.frontiersin.org/article/10.3389/fcvm.2018.00137/fullNaV1.5LQT3Brugada syndromeconductionco-morbidities |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Arie O. Verkerk Arie O. Verkerk Ahmad S. Amin Carol Ann Remme |
spellingShingle |
Arie O. Verkerk Arie O. Verkerk Ahmad S. Amin Carol Ann Remme Disease Modifiers of Inherited SCN5A Channelopathy Frontiers in Cardiovascular Medicine NaV1.5 LQT3 Brugada syndrome conduction co-morbidities |
author_facet |
Arie O. Verkerk Arie O. Verkerk Ahmad S. Amin Carol Ann Remme |
author_sort |
Arie O. Verkerk |
title |
Disease Modifiers of Inherited SCN5A Channelopathy |
title_short |
Disease Modifiers of Inherited SCN5A Channelopathy |
title_full |
Disease Modifiers of Inherited SCN5A Channelopathy |
title_fullStr |
Disease Modifiers of Inherited SCN5A Channelopathy |
title_full_unstemmed |
Disease Modifiers of Inherited SCN5A Channelopathy |
title_sort |
disease modifiers of inherited scn5a channelopathy |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cardiovascular Medicine |
issn |
2297-055X |
publishDate |
2018-10-01 |
description |
To date, a large number of mutations in SCN5A, the gene encoding the pore-forming α-subunit of the primary cardiac Na+ channel (NaV1.5), have been found in patients presenting with a wide range of ECG abnormalities and cardiac syndromes. Although these mutations all affect the same NaV1.5 channel, the associated cardiac syndromes each display distinct phenotypical and biophysical characteristics. Variable disease expressivity has also been reported, where one particular mutation in SCN5A may lead to either one particular symptom, a range of various clinical signs, or no symptoms at all, even within one single family. Additionally, disease severity may vary considerably between patients carrying the same mutation. The exact reasons are unknown, but evidence is increasing that various cardiac and non-cardiac conditions can influence the expressivity and severity of inherited SCN5A channelopathies. In this review, we provide a summary of identified disease entities caused by SCN5A mutations, and give an overview of co-morbidities and other (non)-genetic factors which may modify SCN5A channelopathies. A comprehensive knowledge of these modulatory factors is not only essential for a complete understanding of the diverse clinical phenotypes associated with SCN5A mutations, but also for successful development of effective risk stratification and (alternative) treatment paradigms. |
topic |
NaV1.5 LQT3 Brugada syndrome conduction co-morbidities |
url |
https://www.frontiersin.org/article/10.3389/fcvm.2018.00137/full |
work_keys_str_mv |
AT arieoverkerk diseasemodifiersofinheritedscn5achannelopathy AT arieoverkerk diseasemodifiersofinheritedscn5achannelopathy AT ahmadsamin diseasemodifiersofinheritedscn5achannelopathy AT carolannremme diseasemodifiersofinheritedscn5achannelopathy |
_version_ |
1725342712367939584 |