Author Correction: Long-QT founder variant T309I-Kv7.1 with dominant negative pattern may predispose delayed afterdepolarizations under β-adrenergic stimulation
Autor: | Michal Pásek, Iva Synková, Larisa Chmelikova, Rostislav Navrátil, Renata Gaillyová, Irena Andršová, Olga Švecová, Pavel Vít, Iveta Valášková, Jan Hošek, Markéta Bébarová, Tomáš Novotný |
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Rok vydání: | 2021 |
Předmět: |
Adult
Male Heterozygote medicine.medical_specialty Genotype Science Adrenergic beta-Antagonists Dominant negative Text mining Internal medicine medicine Humans Genetic Predisposition to Disease β adrenergic stimulation Delayed afterdepolarizations Author Correction Genetic Association Studies Multidisciplinary business.industry Genetic Carrier Screening Homozygote Pedigree Europe Long QT Syndrome Phenotype Endocrinology Haplotypes KCNQ1 Potassium Channel Mutation Medicine Female business |
Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-3 (2021) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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