ArticleScientific reports2021
Long-QT founder variant T309I-Kv7.1 with dominant negative pattern may predispose delayed afterdepolarizations under β-adrenergic stimulation.
Article in Scientific reports, 2021. 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 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- C-terminal long-QT type 1 R562S-Kv7.1 variant, the first variant in helix C impairing β-adrenergic response of the slow delayed rectifier K+ channel.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- Role of natural inter-individual variability in the different penetrance of congenital long QT syndromes (LQTS) types 1 and 2: an in silico approach.Scientific reports · 2026Article
- KCNQ1 suppression-replacement gene therapy in transgenic rabbits with type 1 long QT syndrome.European heart journal · 2024Article
- The yield of a comprehensive investigation protocol for the diagnosis of true idiopathic ventricular fibrillation in a real-life clinical setting.Scientific reports · 2024Article
- Deciphering Common Long QT Syndrome Using CRISPR/Cas9 in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes.Frontiers in cardiovascular medicine · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The variant c.926C > T (p.T309I) in KCNQ1 gene was identified in 10 putatively unrelated Czech families with long QT syndrome (LQTS). Mutation carriers (24 heterozygous individuals) were more symptomatic compared to their non-affected relatives (17 individuals). The carriers showed a mild LQTS phenotype including a longer QTc interval at rest (466 ± 24 ms vs. 418 ± 20 ms) and after exercise (508 ± 32 ms vs. 417 ± 24 ms), 4 syncopes and 2 aborted cardiac arrests. The same haplotype associated with the c.926C > T variant was identified in all probands. Using the whole cell patch clamp technique and confocal microscopy, a complete loss of channel function was revealed in the homozygous setting, caused by an impaired channel trafficking. Dominant negativity with preserved reactivity to β-adrenergic stimulation was apparent in the heterozygous setting. In simulations on a human ventricular cell model, the dysfunction resulted in delayed afterdepolarizations (DADs) and premature action potentials under β-adrenergic stimulation that could be prevented by a slight inhibition of calcium current. We conclude that the KCNQ1 variant c.926C > T is the first identified LQTS-related founder mutation in Central Europe. The dominant negative channel dysfunction may lead to DADs under β-adrenergic stimulation. Inhibition of calcium current could be possible therapeutic strategy in LQTS1 patients refractory to β-blocker therapy.
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