Genotype-Phenotype Correlation of
            <i>SCN5A</i>
            Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome

Yamagata, Kenichiro; Horie, Minoru; Aiba, Takeshi; Ogawa, Satoshi; Aizawa, Yoshifusa; Ohe, Tohru; Yamagishi, Masakazu; Makita, Naomasa; Sakurada, Harumizu; Tanaka, Toshihiro; Shimizu, Akihiko; Hagiwara, Nobuhisa; Kishi, Ryoji; Nakano, Yukiko; Takagi, Masahiko; Makiyama, Takeru; Ohno, Seiko; Fukuda, Keiichi; Watanabe, Hiroshi; Morita, Hiroshi; Hayashi, Kenshi; Kusano, Kengo; Kamakura, Shiro; Yasuda, Satoshi; Ogawa, Hisao; Miyamoto, Yoshihiro; Kapplinger, Jamie D.; Ackerman, Michael J.; Shimizu, Wataru

doi:10.1161/circulationaha.117.027983

Cited by 151 publications

(139 citation statements)

References 48 publications

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“…Subsequently, the 45 remaining articles were reviewed for further details, and 28 studies did not meet the inclusion criteria. Finally, 17 studies involving 1780 BrS probands were included in this meta‐analysis …”

Section: Resultsmentioning

confidence: 99%

“…In total, seven studies (four involving Asians, two involving Caucasians and one involving multiple ethnicities) examined the association between the SCN5A mutation status and MAEs during follow up. As shown in Figure , the SCN5A mutation status was associated with an increased risk of MAEs in all BrS patients (OR = 1.78, 95% CI 1.19‐2.26; P = .005).…”

Section: Resultsmentioning

confidence: 99%

“…While more than 20 BrS‐associated genes have been identified, only SCN5A has sufficient genetic evidence suggesting that it is a genetic cause of disease, accounting for 20%‐25% of BrS cases, Despite these advances, genetic testing is still not recommended for BrS risk stratification . Although prior studies have investigated the role of SCN5A mutations in the prevalence, pathogenesis and prognosis of BrS, findings regarding phenotypic feature differences between SCN5A mutation carriers and non‐carriers are inconsistent across studies . Noteworthy, one study suggested that SCN5A mutations are not directly causal to the occurrence of a BrS‐ECG (type I ECG), which indicates that SCN5A status does not always segregate with the phenotype .…”

Section: Introductionmentioning

confidence: 99%

“…Until now, whether the SCN5A mutation status is an independent predictor of risk in BrS still remains controversial. More importantly, some of previous studies included asymptomatic SCN5A ‐positive family members of BrS probands, which might lead to patient selection bias and further alleviate the results because SCN5A mutations seemly do not elevate the arrhythmic risks in asymptomatic patients …”

Section: Introductionmentioning

confidence: 99%

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Brugada syndrome with SCN5A mutations exhibits more pronounced electrophysiological defects and more severe prognosis: A meta‐analysis

et al. 2019

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Whether the presence of SCN5A mutation is a predictor of BrS risk remains controversial, and patient selection bias may have weakened previous findings. Therefore, we performed this study to clarify the clinical characteristics and outcomes of BrS probands with SCN5A mutations. We systematically retrieved eligible studies published through October 2018. A total of 17 studies enrolling 1780 BrS patients were included. Overall, our results found that compared with BrS patients without SCN5A mutations, patients with SCN5A mutations exhibited a younger age at the onset of symptoms and higher rate of the spontaneous type-1 electrocardiogram pattern, more pronounced conduction or repolarization abnormalities, and increased atrial vulnerability. In addition, the presence of SCN5A mutations was associated with an elevated risk of major arrhythmic events in both Asian (odds ratio [OR] = 1.82, 95% confidence interval [CI] 1.07-3.11; P = .03) and Caucasian (OR = 2.24, 95% CI 1.02-4.90; P = .04) populations. In conclusions, patients with SCN5A mutations exhibit more pronounced electrophysiological defects and more severe prognosis.Clinicians should be cautious when utilizing genetic testing for risk stratification or treatment guidance before determining whether the causal relationship regarding SCN5A mutation status is an independent predictor of risk.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Brugada syndrome with SCN5A mutations exhibits more pronounced electrophysiological defects and more severe prognosis: A meta‐analysis

et al. 2019

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“…Dr. Yamagata (National Cerebral and Cardiovascular Center) reported that probands with Brugada syndrome (BrS) and SCN5A mutations had more conduction abnormalities on ECG, and exhibited a higher risk for cardiac events. 11 In the Late Breaking Cohort Studies 4, environmental factors of atrial fibrillation (AF) and treatment were discussed. Dr. Okumura (Hirosaki University) et al combined the data of 5 major AF registries in Japan and estimated significant risk factors for ischemic stroke in non-valvular AF patients.…”

Section: Management Of Arrhythmia: Basic and Clinical Point Of Viewsmentioning

confidence: 99%

Overview of the 81<sup>st</sup> Annual Scientific Meeting of the Japanese Circulation Society　― Cardiovascular Medicine for the Next Generation ―

Fujino

Yoshimuta

Ichida

et al. 2017

Circ J

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SCN5A gene mutations and the risk of ventricular fibrillation and syncope in Brugada syndrome patients: A meta‐analysis

Raharjo

Maulana

Maghfirah

et al. 2018

Journal of Arrhythmia

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Mutations in the gene encoding the main cardiac sodium channel (SCN5A) are the commonest genetic cause of Brugada syndrome (BrS). However, the effect of SCN5A mutations on the outcomes of ventricular fibrillation (VF) and syncope remains uncertain. To clarify this relationship, a meta‐analysis was performed. A comprehensive search was conducted to identify all eligible studies from PubMed, MEDLINE, EBSCO, ProQuest, Science Direct, Clinical Key, and Cochrane database for cohort studies of BrS populations that had been systematically tested for SCN5A mutations. We did meta‐analysis to see the relationship between SCN5A mutations and the occurrence of VF and/or syncope using RevMan 5.3. Five clinical studies met our criteria and included a total of 665 BrS patients. These studies included 45 patients with VF and 178 patients with syncope. We found that in BrS patients with SCN5A mutations the rate of VF event was 30.7% while in patients without mutations was 28.5% (Risk Ratio [RR] = 1.11, [95% CI: 0.61, 2.00], P = 0.73, I 2 = 0%). The occurrence of syncope events was 35.9% in patients with SCN5A mutations and 34.5% in patients without mutations (RR = 1.12, [95% CI: 0.87, 1.45], P = 0.37, I 2 = 39%). Furthermore, the occurrence of combined VF and syncope events were similar between the 2 groups (RR = 1.12, [95% CI: 0.89, 1.42], P = 0.34, I 2 = 11%). BrS patients with SCN5A mutations exhibit a similar risk of future occurence of VF and/or syncope as compared to those without SCN5A mutations.

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Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome

Abstract: Brugada syndrome patients with mutations exhibit more conduction abnormalities on ECG and have higher risk for cardiac events.

Cited by 151 publications

References 48 publications

Brugada syndrome with SCN5A mutations exhibits more pronounced electrophysiological defects and more severe prognosis: A meta‐analysis

Brugada syndrome with SCN5A mutations exhibits more pronounced electrophysiological defects and more severe prognosis: A meta‐analysis

Overview of the 81<sup>st</sup> Annual Scientific Meeting of the Japanese Circulation Society　― Cardiovascular Medicine for the Next Generation ―

SCN5A gene mutations and the risk of ventricular fibrillation and syncope in Brugada syndrome patients: A meta‐analysis

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Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome

Abstract: Brugada syndrome patients with mutations exhibit more conduction abnormalities on ECG and have higher risk for cardiac events.

Cited by 151 publications

References 48 publications

Brugada syndrome with SCN5A mutations exhibits more pronounced electrophysiological defects and more severe prognosis: A meta‐analysis

Brugada syndrome with SCN5A mutations exhibits more pronounced electrophysiological defects and more severe prognosis: A meta‐analysis

Overview of the 81<sup>st</sup> Annual Scientific Meeting of the Japanese Circulation Society ― Cardiovascular Medicine for the Next Generation ―

SCN5A gene mutations and the risk of ventricular fibrillation and syncope in Brugada syndrome patients: A meta‐analysis

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Overview of the 81<sup>st</sup> Annual Scientific Meeting of the Japanese Circulation Society　― Cardiovascular Medicine for the Next Generation ―