Studying Brugada Syndrome With an SCN1B Variants in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
Brugada
channelopathy
genetic
sodium channel
sudden cardiac death
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2019
2019
Historique:
received:
24
08
2019
accepted:
17
10
2019
entrez:
19
11
2019
pubmed:
19
11
2019
medline:
19
11
2019
Statut:
epublish
Résumé
Among rare channelopathies BrS patients are at high risk of sudden cardiac death (SCD). SCN5A mutations are found in a quarter of patients. Other rare gene mutations including SCN1B have been implicated to BrS. Studying the human cellular phenotype of BrS associated with rare gene mutation remains lacking. We sought to study the cellular phenotype of BrS with the SCN1B gene variants using human-induced pluripotent stem cell (hiPSCs)-derived cardiomyocytes (hiPSC-CMs). A BrS patient suffering from recurrent syncope harboring a two variants (c.629T > C and c.637C > A) in SCN1B, which encodes the function-modifying sodium channel beta1 subunit, and three independent healthy subjects were recruited and their skin biopsies were used to generate hiPSCs, which were differentiated into cardiomyocytes (hiPSC-CMs) for studying the cellular electrophysiology. A significantly reduced peak and late sodium channel current (I Our hiPSC-CMs from a BrS-patient with two variants in SCN1B recapitulated some key phenotypic features of BrS and can provide a platform for studies on BrS with SCN1B variants.
Sections du résumé
BACKGROUND
BACKGROUND
Among rare channelopathies BrS patients are at high risk of sudden cardiac death (SCD). SCN5A mutations are found in a quarter of patients. Other rare gene mutations including SCN1B have been implicated to BrS. Studying the human cellular phenotype of BrS associated with rare gene mutation remains lacking.
OBJECTIVES
OBJECTIVE
We sought to study the cellular phenotype of BrS with the SCN1B gene variants using human-induced pluripotent stem cell (hiPSCs)-derived cardiomyocytes (hiPSC-CMs).
METHODS AND RESULTS
RESULTS
A BrS patient suffering from recurrent syncope harboring a two variants (c.629T > C and c.637C > A) in SCN1B, which encodes the function-modifying sodium channel beta1 subunit, and three independent healthy subjects were recruited and their skin biopsies were used to generate hiPSCs, which were differentiated into cardiomyocytes (hiPSC-CMs) for studying the cellular electrophysiology. A significantly reduced peak and late sodium channel current (I
CONCLUSION
CONCLUSIONS
Our hiPSC-CMs from a BrS-patient with two variants in SCN1B recapitulated some key phenotypic features of BrS and can provide a platform for studies on BrS with SCN1B variants.
Identifiants
pubmed: 31737628
doi: 10.3389/fcell.2019.00261
pmc: PMC6839339
doi:
Types de publication
Journal Article
Langues
eng
Pagination
261Informations de copyright
Copyright © 2019 El-Battrawy, Müller, Zhao, Cyganek, Zhong, Zhang, Kleinsorge, Lan, Li, Xu, Huang, Liao, Moscu-Gregor, Albers, Dinkel, Lang, Diecke, Zimmermann, Utikal, Wieland, Borggrefe, Zhou and Akin.
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