ArticleCardiovascular research2015
Role of common and rare variants in SCN10A: results from the Brugada syndrome QRS locus gene discovery collaborative study.
Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 64 papers.
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64 citing papers in PubMed, 106 citations in OpenAlex.
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- Peripheral temperature dysregulation associated with functionally altered NaPflugers Archiv : European journal of physiology · 2023Article
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- Brugada Syndrome: More than a Monogenic Channelopathy.Biomedicines · 2023Review
- Transcriptional Dysregulation Underlies Both Monogenic Arrhythmia Syndrome and Common Modifiers of Cardiac Repolarization.Circulation · 2023Article
- Brugada Syndrome: From Molecular Mechanisms and Genetics to Risk Stratification.International journal of molecular sciences · 2023Review
- Concealed Substrates in Brugada Syndrome: Isolated Channelopathy or Associated Cardiomyopathy?Genes · 2022Review
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- Common variants in SCN10A gene associated with Brugada syndrome.Human molecular genetics · 2021Article
- Personalized medicine in cardiovascular disease: review of literature.Journal of diabetes and metabolic disorders · 2021Review
- Ventricular voltage-gated ion channels: Detection, characteristics, mechanisms, and drug safety evaluation.Clinical and translational medicine · 2021Review
- The physiological function of different voltage-gated sodium channels in pain.Nature reviews. Neuroscience · 2021Review
- Analysis of Brugada syndrome loci reveals that fine-mapping clustered GWAS hits enhances the annotation of disease-relevant variants.Cell reports. Medicine · 2021Article
- iPSC-Cardiomyocyte Models of Brugada Syndrome-Achievements, Challenges and Future Perspectives.International journal of molecular sciences · 2021Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
33 authors at 14 institutions in 7 countries.
Funding
Abstract
aimsBrugada syndrome (BrS) remains genetically heterogeneous and is associated with slowed cardiac conduction. We aimed to identify genetic variation in BrS cases at loci associated with QRS duration. METHODS AND
resultsA multi-centre study sequenced seven candidate genes (SCN10A, HAND1, PLN, CASQ2, TKT, TBX3, and TBX5) in 156 Caucasian SCN5A mutation-negative BrS patients (80% male; mean age 48) with symptoms (64%) and/or a family history of sudden death (47%) or BrS (18%). Forty-nine variants were identified: 18 were rare (MAF <1%) and non-synonymous; and 11/18 (61.1%), mostly in SCN10A, were predicted as pathogenic using multiple bioinformatics tools. Allele frequencies were compared with the Exome Sequencing and UK10K Projects. SKAT methods tested rare variation in SCN10A finding no statistically significant difference between cases and controls. Co-segregation analysis was possible for four of seven probands carrying a novel pathogenic variant. Only one pedigree (I671V/G1299A in SCN10A) showed co-segregation. The SCN10A SNP V1073 was, however, associated strongly with BrS [66.9 vs. 40.1% (UK10K) OR (95% CI) = 3.02 (2.35-3.87), P = 8.07 × 10-19]. Voltage-clamp experiments for NaV1.8 were performed for SCN10A common variants V1073, A1073, and rare variants of interest: A200V and I671V. V1073, A200V and I671V, demonstrated significant reductions in peak INa compared with ancestral allele A1073 (rs6795970).
conclusionRare variants in the screened QRS-associated genes (including SCN10A) are not responsible for a significant proportion of SCN5A mutation negative BrS. The common SNP SCN10A V1073 was strongly associated with BrS and demonstrated loss of NaV1.8 function, as did rare variants in isolated patients.
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