ArticleHeart rhythm2012
A novel rare variant in SCN1Bb linked to Brugada syndrome and SIDS by combined modulation of Na(v)1.5 and K(v)4.3 channel currents.
Article in Heart rhythm, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 102 citations in OpenAlex.
- Enhanced risk profiling of implanted defibrillator shocks with circulating SCN5A mRNA splicing variants: a pilot trial.Journal of the American College of Cardiology · 2014Trial
- Heterozygous Loss of Scn1b Results in Concealed Conduction Phenotype Unmasked by Osmotic Stress.bioRxiv : the preprint server for biology · 2026Article
- Genetic Basis of Brugada Syndrome.Biomedicines · 2025Review
- New focus on cardiac voltage-gated sodium channel β1 and β1B: Novel targets for treating and understanding arrhythmias?Heart rhythm · 2025Review
- The Kir2.1E299V mutation increases atrial fibrillation vulnerability while protecting the ventricles against arrhythmias in a mouse model of short QT syndrome type 3.Cardiovascular research · 2024Article
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- Transcriptional Dysregulation Underlies Both Monogenic Arrhythmia Syndrome and Common Modifiers of Cardiac Repolarization.Circulation · 2023Article
- Genomic and Non-Genomic Regulatory Mechanisms of the Cardiac Sodium Channel in Cardiac Arrhythmias.International journal of molecular sciences · 2022Review
- Review
- Molecular Pathology of Sodium Channel Beta-Subunit Variants.Frontiers in pharmacology · 2021Article
- Comprehensive Analysis of Genes Associated With Sudden Infant Death Syndrome.Frontiers in pediatrics · 2021Article
- The role of sodium channels in sudden unexpected death in pediatrics.Molecular genetics & genomic medicine · 2020Article
- Cell-Adhesion Properties of β-Subunits in the Regulation of Cardiomyocyte Sodium Channels.Biomolecules · 2020Review
- Brugada Syndrome: Oligogenic or Mendelian Disease?International journal of molecular sciences · 2020Review
- Structures Illuminate Cardiac Ion Channel Functions in Health and in Long QT Syndrome.Frontiers in pharmacology · 2020Review
- AnFrontiers in cell and developmental biology · 2020Article
- Studying Brugada Syndrome With an SCN1B Variants in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Frontiers in cell and developmental biology · 2019Article
- SCN1Bβ mutations that affect their association with Kv4.3 underlie early repolarization syndrome.Journal of cellular and molecular medicine · 2018Article
- Genetics of Atrial Fibrillation.Journal of the American Heart Association · 2018Review
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Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundCardiac sodium channel β-subunit mutations have been associated with several inherited cardiac arrhythmia syndromes.
objectiveTo identify and characterize variations in SCN1Bb associated with Brugada syndrome (BrS) and sudden infant death syndrome (SIDS).
methodsAll known exons and intron borders of the BrS-susceptibility genes were amplified and sequenced in both directions. Wild type (WT) and mutant genes were expressed in TSA201 cells and studied using co-immunoprecipitation and whole-cell patch-clamp techniques.
resultsPatient 1 was a 44-year-old man with an ajmaline-induced type 1 ST-segment elevation in V1 and V2 supporting the diagnosis of BrS. Patient 2 was a 62-year-old woman displaying a coved-type BrS electrocardiogram who developed cardiac arrest during fever. Patient 3 was a 4-month-old female SIDS case. A R214Q variant was detected in exon 3A of SCN1Bb (Na(v)1B) in all three probands, but not in any other gene previously associated with BrS or SIDS. R214Q was identified in 4 of 807 ethnically-matched healthy controls (0.50%). Co-expression of SCN5A/WT + SCN1Bb/R214Q resulted in peak sodium channel current (I(Na)) 56.5% smaller compared to SCN5A/WT + SCN1Bb/WT (n = 11-12, P<0.05). Co-expression of KCND3/WT + SCN1Bb/R214Q induced a Kv4.3 current (transient outward potassium current, I(to)) 70.6% greater compared with KCND3/WT + SCN1Bb/WT (n = 10-11, P<0.01). Co-immunoprecipitation indicated structural association between Na(v)β1B and Na(v)1.5 and K(v)4.3.
conclusionOur results suggest that R214Q variation in SCN1Bb is a functional polymorphism that may serve as a modifier of the substrate responsible for BrS or SIDS phenotypes via a combined loss of function of sodium channel current and gain of function of transient outward potassium current.
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