A novel mutation in the SCN5A gene is associated with Brugada syndrome

Shin, Dong Jik; Kim, Eunmin; Park, Sang Bum; Jang, Woncheol; Bae, Yu Jeong; Han, Ji-Hye; Jang, Yangsoo; Joung, Boyoung; Lee, Moon Hyoung; Kim, Sung Soon; Huang, Hai; Chahine, Mohamed; Yoon, Sungjoo Kim

doi:10.1016/j.lfs.2006.10.025

Cited by 13 publications

(4 citation statements)

References 41 publications

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“…Because it produces a protein with a truncation of more than a half of the WT cardiac sodium channel protein, the observation that it elicited no current was reasonable. In constancy with our founding, Shin et al reported a mutation, W1119X, which lacked even less amino acids than p.I848fs, failed to generate any current[ 14 ]. Moreover, by western blotting and confocal imaging analysis, the presence of p.I848fs at cytoplasmic membrane suggested that the remained amino acid residues in I848fs were sufficient for the processing and trafficking of cardiac sodium channel.…”

Section: Discussionsupporting

confidence: 82%

Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations

et al. 2009

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The Brugada syndrome is characterized by ST segment elevation in the right precodial leads V1-V3 on surface ECG accompanied by episodes of ventricular fibrillation causing syncope or even sudden death. The molecular and cellular mechanisms that lead to Brugada syndrome are not yet completely understood. However, SCN5A is the most well known responsible gene that causes Brugada syndrome. Until now, more than a hundred mutations in SCN5A responsible for Brugada syndrome have been described. Functional studies of some of the mutations have been performed and show that a reduction of human cardiac sodium current accounts for the pathogenesis of Brugada syndrome. Here we reported three novel SCN5A mutations identified in patients with Brugada syndrome in Taiwan (p.I848fs, p.R965C, and p.1876insM). Their electrophysiological properties were altered by patch clamp analysis. The p.I848fs mutant generated no sodium current. The p.R965C and p.1876insM mutants produced channels with steady state inactivation shifted to a more negative potential (9.4 mV and 8.5 mV respectively), and slower recovery from inactivation. Besides, the steady state activation of p.1876insM was altered and was shifted to a more positive potential (7.69 mV). In conclusion, the SCN5A channel defect related to Brugada syndrome might be diverse but all resulted in a decrease of sodium current.

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Section: Discussionsupporting

confidence: 82%

Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations

et al. 2009

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“…10 The W1191X mutation is one of these loss-of-function mutations. 11 This nonsense mutation results in a glycine to alanine substitution leading to a premature stop codon at amino acid position 1191. 11 W1191X has been implicated in BrS, long QT syndrome subtype 3, and cardiac conduction disturbance.…”

Section: Discussionmentioning

confidence: 99%

Ventricular fibrillation in Graves disease reveals a rare SCN5A mutation with W1191X variant associated with Brugada syndrome

Stawiarski

Clarke

Pollack

et al. 2021

HeartRhythm Case Reports

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“…When these mutant channels were heterozygously expressed with wild type channels, a 50% reduction of sodium current was detected. This reduction, together with the absence of effects on activation or inactivation properties or on current kinetics, indicated that only the wild type channels were functiona [60].…”

Section: Expression Systemsmentioning

confidence: 99%

Experimental Models of Brugada syndrome

Sendfeld

Selga

Scornik

et al. 2019

IJMS

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Brugada syndrome is an inherited, rare cardiac arrhythmogenic disease, associated with sudden cardiac death. It accounts for up to 20% of sudden deaths in patients without structural cardiac abnormalities. The majority of mutations involve the cardiac sodium channel gene SCN5A and give rise to classical abnormal electrocardiogram with ST segment elevation in the right precordial leads V1 to V3 and a predisposition to ventricular fibrillation. The pathophysiological mechanisms of Brugada syndrome have been investigated using model systems including transgenic mice, canine heart preparations, and expression systems to study different SCN5A mutations. These models have a number of limitations. The recent development of pluripotent stem cell technology creates an opportunity to study cardiomyocytes derived from patients and healthy individuals. To date, only a few studies have been done using Brugada syndrome patient-specific iPS-CM, which have provided novel insights into the mechanisms and pathophysiology of Brugada syndrome. This review provides an evaluation of the strengths and limitations of each of these model systems and summarizes the key mechanisms that have been identified to date.

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A novel mutation in the SCN5A gene is associated with Brugada syndrome

Cited by 13 publications

References 41 publications

Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations

Distinct functional defect of three novel Brugada syndrome related cardiac sodium channel mutations

Ventricular fibrillation in Graves disease reveals a rare SCN5A mutation with W1191X variant associated with Brugada syndrome

Experimental Models of Brugada syndrome

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