ArticleJournal of the American College of Cardiology2021
Distinct Features of Probands With Early Repolarization and Brugada Syndromes Carrying SCN5A Pathogenic Variants.
Article in Journal of the American College of Cardiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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17 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- The SCN5A Gene Is a Predictor of Phenotype Severity in Brugada Syndrome: A Comprehensive Literature Review.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2023Pooled it
- Review
- A cardiac sodium channelopathy overlap syndrome presenting as stroke in a young child.HeartRhythm case reports · 2026Article
- Contemporary Perspectives on J-Wave Syndromes: An Expert Consensus Statement.Journal of arrhythmia · 2026Article
- Exploring sex-specific clinical features in Chinese patients with Takotsubo syndrome.BMC cardiovascular disorders · 2025Article
- Risk stratification of major arrhythmia events in Japanese patients with Brugada syndrome using machine learning models.Heart rhythm O2 · 2025Article
- Characterization of novel arrhythmogenic patterns arising secondary to heterogeneous expression and activation of Nav1.8.Frontiers in cardiovascular medicine · 2025Article
- Primary Electrical Heart Disease-Principles of Pathophysiology and Genetics.International journal of molecular sciences · 2024Review
- Human Genetics of Cardiac Arrhythmias.Advances in experimental medicine and biology · 2024Review
- Brugada Syndrome: A Comprehensive Review of Fundamental and Electrophysiological New Findings.Journal of clinical medicine · 2023Review
- Functional identification of hot-spot mutations in cardiac calcium channel genes associated with the J wave syndromes.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Article
- NovelExperimental and therapeutic medicine · 2023Article
- Subepicardial Cardiomyopathy: A Disease Underlying J-Wave Syndromes and Idiopathic Ventricular Fibrillation.Circulation · 2023Article
- The Utility of Sodium Channel Provocation in Unexplained Cardiac Arrest Survivors and Electrocardiographic Predictors of Ventricular Fibrillation Recurrence.Circulation. Arrhythmia and electrophysiology · 2022Article
- European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2022Article
- European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases.Journal of arrhythmia · 2022Article
- Pathogenesis and Management of Brugada Syndrome: Recent Advances and Protocol for Umbrella Reviews of Meta-Analyses in Major Arrhythmic Events Risk Stratification.Journal of clinical medicine · 2022Review
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16 authors at 8 institutions in 5 countries.
Funding
Abstract
backgroundTwo major forms of inherited J-wave syndrome (JWS) are recognized: early repolarization syndrome (ERS) and Brugada syndrome (BrS).
objectivesThis study sought to assess the distinct features between patients with ERS and BrS carrying pathogenic variants in SCN5A.
methodsClinical evaluation and next-generation sequencing were performed in 262 probands with BrS and 104 with ERS. Nav1.5 and Kv4.3 channels were studied with the use of patch-clamp techniques. A computational model was used to investigate the protein structure.
resultsThe SCN5A+ yield in ERS was significantly lower than in BrS (9.62% vs 22.90%; P = 0.004). Patients diagnosed with ERS displayed shorter QRS and QTc than patients with BrS. More than 2 pathogenic SCN5A variants were found in 5 probands. These patients displayed longer PR intervals and QRS duration and experienced more major arrhythmia events (MAE) compared with those carrying only a single pathogenic variant. SCN5A-L1412F, detected in a fever-induced ERS patient, led to total loss of function, destabilized the Nav1.5 structure, and showed a dominant-negative effect, which was accentuated during a febrile state. ERS-related SCN5A-G452C did not alter the inward sodium current (INa) when SCN5A was expressed alone, but when coexpressed with KCND3 it reduced peak INa by 44.52% and increased the transient outward potassium current (Ito) by 106.81%.
conclusionsThese findings point to SCN5A as a major susceptibility gene in ERS as much as it is in BrS, whereas the lower SCN5A+ ratio in ERS indicates the difference in underlying electrophysiology. These findings also identify the first case of fever-induced ERS and demonstrate a critical role of Ito in JWS and a higher risk for MAE in JWS probands carrying multiple pathogenic variants in SCN5A.
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