ArticleClinical and translational science2010
SCN5A rare variants in familial dilated cardiomyopathy decrease peak sodium current depending on the common polymorphism H558R and common splice variant Q1077del.
Article in Clinical and translational science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Variability in reported midpoints of (in)activation of cardiac INa.The Journal of general physiology · 2025Pooled it
- The disease-specific phenotype in cardiomyocytes derived from induced pluripotent stem cells of two long QT syndrome type 3 patients.PloS one · 2013Trial
- Left Ventricular Noncompaction Cardiomyopathy in Children: A Focus on Genetic and Molecular Mechanisms.Reviews in cardiovascular medicine · 2025Review
- Multifocal ectopic purkinje-related premature contractions and related cardiomyopathy.Frontiers in cardiovascular medicine · 2023Review
- Determining the Likelihood of Disease Pathogenicity Among Incidentally Identified Genetic Variants in Rare Dilated Cardiomyopathy-Associated Genes.Journal of the American Heart Association · 2022Article
- Article
- Identification ofInternational journal of molecular sciences · 2021Article
- Burden of Cardiomyopathic Genetic Variation in Lethal Pediatric Myocarditis.Circulation. Genomic and precision medicine · 2021Article
- SCN5A variant R222Q generated abnormal changes in cardiac sodium current and action potentials in murine myocytes and Purkinje cells.Heart rhythm · 2019Article
- Cardiac Sodium Channel Dysfunction and Dilated Cardiomyopathy: A Contemporary Reappraisal of Pathophysiological Concepts.Journal of clinical medicine · 2019Article
- A leaky voltage sensor domain of cardiac sodium channels causes arrhythmias associated with dilated cardiomyopathy.Scientific reports · 2018Article
- A common polymorphism in the SCN5A gene is associated with dilated cardiomyopathy.Journal of cardiovascular medicine (Hagerstown, Md.) · 2018Article
- Rapid and effective response of the R222Q SCN5A to quinidine treatment in a patient with Purkinje-related ventricular arrhythmia and familial dilated cardiomyopathy: a case report.BMC medical genetics · 2018Article
- Disease Modifiers of InheritedFrontiers in cardiovascular medicine · 2018Review
- H558R, a common SCN5A polymorphism, modifies the clinical phenotype of Brugada syndrome by modulating DNA methylation of SCN5A promoters.Journal of biomedical science · 2017Article
- Analysis of SCN5A Gene Variants in East Slovak Patients with Cardiomyopathy.Journal of clinical laboratory analysis · 2017Article
- Beyond the Electrocardiogram: Mutations in Cardiac Ion Channel Genes Underlie Nonarrhythmic Phenotypes.Clinical Medicine Insights. Cardiology · 2017Review
- Further Insights in the Most Common SCN5A Mutation Causing Overlapping Phenotype of Long QT Syndrome, Brugada Syndrome, and Conduction Defect.Journal of the American Heart Association · 2016Article
- The biophysical characterization of the first SCN5A mutation R1512W identified in Chinese sudden unexplained nocturnal death syndrome.Medicine · 2016Observational
- Identification of novel mutations including a double mutation in patients with inherited cardiomyopathy by a targeted sequencing approach using the Ion Torrent PGM system.International journal of molecular medicine · 2016Article
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9 authors.
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Abstract
Obtaining functional data with newly identified rare variants increases certainty that the variant identified is relevant for dilated cardiomyopathy (DCM) causation. Two novel SCN5A rare variants, R222Q and I1835T, segregated with DCM in two families with affected individuals homozygous or heterozygous for the common SCN5A polymorphism H558R. cDNAs with each rare variant were constructed in the common Q1077del or Q1077 splice variant backgrounds with and without the H558R polymorphism and expressed in HEK293 cells. Sodium current (I(Na) ) was studied for each using whole-cell voltage clamp. In the Q1077del background I(Na) densities of R222Q and I1835T were not different from wild type, but the combined variants of R222Q/H558R, I1835T/H558R caused approximately 35% and approximately 30% reduction, respectively, and each showed slower recovery from inactivation. In the Q1077del background R222Q and R222Q/H558R also exhibited a significant negative shift in both activation and inactivation while I1835T/H558R showed a significant negative shift in inactivation that tended to decrease window current. In contrast, expression in the Q1077 background showed no changes in peak I(Na) densities, decay, or recovery from inactivation for R222Q/H558R and I1835T/H558R. We conclude that the biophysical findings, dependent upon common SCN5A variants, provide further evidence that these novel SCN5A rare variants are relevant for DCM.
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