SCN5A mutation identified in a patient with short-coupled variant of torsades de pointes.
SCN5A
ScTdP
genetics
inherited arrhythmia
ion channel
Journal
Pacing and clinical electrophysiology : PACE
ISSN: 1540-8159
Titre abrégé: Pacing Clin Electrophysiol
Pays: United States
ID NLM: 7803944
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
10
12
2019
revised:
27
03
2020
accepted:
19
04
2020
pubmed:
24
4
2020
medline:
19
5
2021
entrez:
24
4
2020
Statut:
ppublish
Résumé
Short-coupled variant of torsades de pointes (scTdP) is a disease characterized by TdP without QT prolongation, which is initiated by extremely short-coupled ventricular extra-systoles. Its genetic background remains rarely unveiled. We aimed to identify genetic variations in patients with scTdP and to analyze the functional change of the mutant Na We performed genetic analysis for inherited arrhythmia-related 45 genes using next-generation sequencer (MiSeq, Illumina) among seven consecutive scTdP patients. We identified an SCN5A mutation R800H in a 38-year-old male who suffered ventricular fibrillation during dinner and was resuscitated. Two months later, he lost his consciousness at work. His Holter electrocardiogram showed scTdP. He had no family history of sudden cardiac death or heart disease. Functional analysis of the SCN5A-R800H channels showed a significantly shortened recovery time from inactivation. Peak sodium current densities in SCN5A-R800H were larger than those in wild type but the difference was not statistically significant. We identified an SCN5A mutation in a scTdP patient and confirmed that the mutant channel caused the shortness of recovery time from inactivation. SCN5A might be a candidate gene for scTdP.
Sections du résumé
BACKGROUND
Short-coupled variant of torsades de pointes (scTdP) is a disease characterized by TdP without QT prolongation, which is initiated by extremely short-coupled ventricular extra-systoles. Its genetic background remains rarely unveiled.
OBJECTIVE
We aimed to identify genetic variations in patients with scTdP and to analyze the functional change of the mutant Na
METHODS AND RESULTS
We performed genetic analysis for inherited arrhythmia-related 45 genes using next-generation sequencer (MiSeq, Illumina) among seven consecutive scTdP patients. We identified an SCN5A mutation R800H in a 38-year-old male who suffered ventricular fibrillation during dinner and was resuscitated. Two months later, he lost his consciousness at work. His Holter electrocardiogram showed scTdP. He had no family history of sudden cardiac death or heart disease. Functional analysis of the SCN5A-R800H channels showed a significantly shortened recovery time from inactivation. Peak sodium current densities in SCN5A-R800H were larger than those in wild type but the difference was not statistically significant.
CONCLUSIONS
We identified an SCN5A mutation in a scTdP patient and confirmed that the mutant channel caused the shortness of recovery time from inactivation. SCN5A might be a candidate gene for scTdP.
Substances chimiques
NAV1.5 Voltage-Gated Sodium Channel
0
SCN5A protein, human
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
456-461Informations de copyright
© 2020 Wiley Periodicals, Inc.
Références
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