ArticlePhysiological reports2022
Characterization of the mechanism by which a nonsense variant in RYR2 leads to disordered calcium handling.
Article in Physiological reports, 2022. 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 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- Calcium release deficiency syndrome: an emerging ryanodinopathy.Frontiers in molecular biosciences · 2026Review
- Catecholaminergic polymorphic ventricular tachycardia: A narrative review of recent advances in genetics, mechanisms, diagnosis, and treatment.Asian heart journal · 2025Review
- Expression assay of calcium signaling related lncRNAs in autism.Molecular biology reports · 2024Article
- The Landscape of Point Mutations in Human Protein Coding Genes Leading to Pregnancy Loss.International journal of molecular sciences · 2023Review
- Article
- Construction of a risk scoring system using clinical factors andFrontiers in pharmacology · 2023Article
- Erratum: Characterization of the mechanism by which a nonsense variant in RYR2 leads to disordered calcium handling.Physiological reports · 2022Article
- Characterization of the mechanism by which a nonsense variant in RYR2 leads to disordered calcium handling.Physiological reports · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
Heterozygous missense variants of the cardiac ryanodine receptor gene (RYR2) cause catecholaminergic polymorphic ventricular tachycardia (CPVT). These missense variants of RYR2 result in a gain of function of the ryanodine receptors, characterized by increased sensitivity to activation by calcium that results in an increased propensity to develop calcium waves and delayed afterdepolarizations. We have recently detected a nonsense variant in RYR2 in a young patient who suffered an unexplained cardiac arrest. To understand the mechanism by which this variant in RYR2, p.(Arg4790Ter), leads to ventricular arrhythmias, human induced pluripotent stem cells (hiPSCs) harboring the novel nonsense variant in RYR2 were generated and differentiated into cardiomyocytes (RYR2-hiPSC-CMs) and molecular and calcium handling properties were studied. RYR2-hiPSC-CMs displayed significant calcium handling abnormalities at baseline and following treatment with isoproterenol. Treatment with carvedilol and nebivolol resulted in a significant reduction in calcium handling abnormalities in the RYR2-hiPSC-CMs. Expression of the mutant RYR2 allele was confirmed at the mRNA level and partial silencing of the mutant allele resulted in a reduction in calcium handling abnormalities at baseline. The nonsense variant behaves similarly to other gain of function variants in RYR2. Carvedilol and nebivolol may be suitable treatments for patients with gain of function RYR2 variants.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.