ArticleMolecular genetics & genomic medicine2019
Penetrance and expressivity of the R858H CACNA1C variant in a five-generation pedigree segregating an arrhythmogenic channelopathy.
Article in Molecular genetics & genomic medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Geno- and phenotypic characteristics and clinical outcomes ofFrontiers in cardiovascular medicine · 2022Pooled it
- Timothy syndrome and CACNA1C-Related Disorder: first international language and management guidelines consensus statement.European journal of human genetics : EJHG · 2026Review
- Monogenic Syndromes as a Cause of Adverse Drug Reactions in the Russian Population.International journal of molecular sciences · 2026Article
- Genome x Environment analysis of Sudden Unexpected Infant Death unveils etiologic heterogeneity and strong cannabis and genetic disease risks.medRxiv : the preprint server for health sciences · 2025Article
- Timothy Syndrome and CACNA1C-Related Disorder: First International Language and Management Guidelines Consensus Statement.Research square · 2025Article
- Calmodulin D133H Disrupts CaCells · 2025Article
- Arrhythmogenic calmodulin variants D131E and Q135P disrupt interaction with the L-type voltage-gated CaActa physiologica (Oxford, England) · 2025Article
- Research Progress on Natural Products' Therapeutic Effects on Atrial Fibrillation by Regulating Ion Channels.Cardiovascular therapeutics · 2022Review
- Article
- An interactive analysis of the mouse oviductal miRNA profiles.Frontiers in cell and developmental biology · 2022Article
- The Interface of Nuclear and Membrane Steroid Signaling.Endocrinology · 2021Review
- Update on the Molecular Genetics of Timothy Syndrome.Frontiers in pediatrics · 2021Review
- Penetrance and expressivity of the R858H CACNA1C variant in a five-generation pedigree segregating an arrhythmogenic channelopathy.Molecular genetics & genomic medicine · 2019Article
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIsolated cardiac arrhythmia due to a variant in CACNA1C is of recent knowledge. Most reports have been of singleton cases or of quite small families, and estimates of penetrance and expressivity have been difficult to obtain. We here describe a large pedigree, from which such estimates have been calculated.
methodsWe studied a five-generation family, in which a CACNA1C variant c.2573G>A p.Arg858His co-segregates with syncope and cardiac arrest, documenting electrocardiographic data and cardiac symptomatology. The reported patients/families from the literature with CACNA1C gene variants were reviewed, and genotype-phenotype correlations are drawn.
resultsThe range of phenotype in the studied family is wide, from no apparent effect, through an asymptomatic QT interval prolongation on electrocardiography, to episodes of presyncope and syncope, ventricular fibrillation, and sudden death. QT prolongation showed inconsistent correlation with functional cardiology. Based upon analysis of 28 heterozygous family members, estimates of penetrance and expressivity are derived.
conclusionsThese estimates of penetrance and expressivity, for this specific variant, may be useful in clinical practice. Review of the literature indicates that individual CACNA1C variants have their own particular genotype-phenotype correlations. We suggest that, at least in respect of the particular variant reported here, "arrhythmogenic channelopathy" may be a more fitting nomenclature than long QT syndrome.
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