ArticlePloS one2017
A mutation in the CACNA1C gene leads to early repolarization syndrome with incomplete penetrance: A Chinese family study.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern.JCI insight · 2019Pooled it
- Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.Cell discovery · 2025Review
- Primary Electrical Heart Disease-Principles of Pathophysiology and Genetics.International journal of molecular sciences · 2024Review
- Clinical Genetics of Inherited Arrhythmogenic Disease in the Pediatric Population.Biomedicines · 2022Review
- Clinical and Functional Genetic Characterization of the Role of Cardiac Calcium Channel Variants in the Early Repolarization Syndrome.Frontiers in cardiovascular medicine · 2021Article
- Early repolarization pattern associated with coronary artery disease and increased the risk of cardiac death in acute myocardium infarction.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2020Article
- Penetrance and expressivity of the R858H CACNA1C variant in a five-generation pedigree segregating an arrhythmogenic channelopathy.Molecular genetics & genomic medicine · 2019Article
- Expanding clinical phenotype in CACNA1C related disorders: From neonatal onset severe epileptic encephalopathy to late-onset epilepsy.American journal of medical genetics. Part A · 2018Article
- Evaluation of a Potential Clinical Significant Drug-Drug Interaction between Digoxin and Bupropion in Cynomolgus Monkeys.Pharmaceutical research · 2018Article
- Gene and Protein Expression Profile of Selected Molecular Targets Mediating Electrophysiological Function inInternational journal of molecular sciences · 2018Article
- SCN1Bβ mutations that affect their association with Kv4.3 underlie early repolarization syndrome.Journal of cellular and molecular medicine · 2018Article
- An African loss-of-function CACNA1C variant p.T1787M associated with a risk of ventricular fibrillation.Scientific reports · 2018Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEarly repolarization syndrome (ERS) may be a near-Mendelian or an oligogenic disease; however, no direct evidence has been provided to support this theory. METHODS AND
resultsWe described a large Chinese family with nocturnal sudden cardiac death induced by ERS in most of the young male adults. One missense mutation (p.Q1916R) was found in the major subunit of the L-type calcium channel gene CACNA1C by the direct sequencing of candidate genes. A concomitant gain-of-function variant in the sodium channel gene SCN5A (p.R1193Q) was found to rescue the phenotype of the female CACNA1C-Q1916R mutation carriers, which led to the incomplete penetrance. The functional studies, via the exogenous expression approach, revealed that the CACNA1C-Q1916R mutation led to a decreasing L-type calcium current and the protein expression defect. The decreased calcium current produced by the mutant channel was improved by isoproterenol but exacerbated by testosterone. The effects of CACNA1C-Q1916R mutation and testosterone on cellular electrophysiology were further confirmed by the human ventricular action potential simulation.
conclusionsOur results demonstrated that the loss-of-function CACNA1C-Q1916R mutation contributed to ERS-related sudden cardiac death, and the phenotypic incomplete penetrance was modified by the SCN5A-R1193Q variant and sex. These findings suggest that phenotypes of ERS are modified by multiple genetic factors, which supports the theory that ERS may be an oligogenic disease.
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