ArticleHeart rhythm2011
R231C mutation in KCNQ1 causes long QT syndrome type 1 and familial atrial fibrillation.
Article in Heart rhythm, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 72 citations in OpenAlex.
- Barium senses subtle pore changes in a voltage-gated KScience advances · 2026Article
- Supraventricular tachycardias in ion channel diseases.Herzschrittmachertherapie & Elektrophysiologie · 2026Review
- A physiologically-relevant intermediate state structure of a voltage-gated potassium channel.Nature communications · 2025Article
- Activation of Small Conductance CaInternational journal of molecular sciences · 2025Article
- Atrial fibrillation and risk of sudden cardiac arrest in young adults.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 · 2024Article
- NovelFrontiers in physiology · 2024Article
- Mutation-Specific Differences in Kv7.1 (International journal of molecular sciences · 2022Review
- GENESIS: Gene-Specific Machine Learning Models for Variants of Uncertain Significance Found in Catecholaminergic Polymorphic Ventricular Tachycardia and Long QT Syndrome-Associated Genes.Circulation. Arrhythmia and electrophysiology · 2022Article
- Review
- Functional testing for variant prioritization in a family with long QT syndrome.Molecular genetics and genomics : MGG · 2021Article
- Arrhythmogenic Effects of Genetic Mutations Affecting Potassium Channels in Human Atrial Fibrillation: A Simulation Study.Frontiers in physiology · 2021Article
- Insights into Cardiac IKs (KCNQ1/KCNE1) Channels Regulation.International journal of molecular sciences · 2020Review
- Collision-Induced Unfolding Differentiates Functional Variants of the KCNQ1 Voltage Sensor Domain.Journal of the American Society for Mass Spectrometry · 2020Article
- Epilepsy-associated mutations in the voltage sensor of KCNQ3 affect voltage dependence of channel opening.The Journal of general physiology · 2019Article
- Action potential shortening rescues atrial calcium alternans.The Journal of physiology · 2019Article
- Investigating the Complex Arrhythmic Phenotype Caused by the Gain-of-Function Mutation KCNQ1-G229D.Frontiers in physiology · 2019Article
- High-Throughput Functional Evaluation of KCNQ1 Decrypts Variants of Unknown Significance.Circulation. Genomic and precision medicine · 2018Article
- Genetics of Atrial Fibrillation.Journal of the American Heart Association · 2018Review
- Molecular Pathophysiology of Congenital Long QT Syndrome.Physiological reviews · 2017Review
- The Promise and Peril of Precision Medicine: Phenotyping Still Matters Most.Mayo Clinic proceedings · 2016Review
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundLoss-of-function mutations in the gene KCNQ1 encoding the Kv7.1 K(+) channel cause long QT syndrome type 1 (LQT1), whereas gain-of-function mutations are associated with short QT syndrome as well as familial atrial fibrillation (FAF). However, KCNQ1 mutation pleiotropy, which is capable of expressing both LQT1 and FAF, has not been demonstrated for a discrete KCNQ1 mutation. The genotype-phenotype relationship for a family with FAF suggests a possible association with the LQT1 p.Arg231Cys-KCNQ1 (R231C-Q1) mutation.
objectiveThe purpose of this study was to determine whether R231C-Q1 also can be linked to FAF.
methodsThe R231C-Q1 proband with AF underwent genetic testing for possible mutations in 10 other AF-linked genes plus KCNH2 and SCN5A. Sixteen members from five other R231C-positive LQT1 families were genetically tested for 21 single nucleotide polymorphisms (SNPs) to determine if the FAF family had discriminatory SNPs associated with AF. R231C-Q1 was expressed with KCNE1 (E1) in HEK293 cells, and Q1E1 currents (I(Q1E1)) were analyzed using the whole-cell patch-clamp technique.
resultsGenetic analyses revealed no additional mutations or discriminatory SNPs. Cells expressing WT-Q1 and R231C-Q1 exhibited some constitutively active I(Q1E1) and smaller maximal I(Q1E1) compared to cells expressing WT-Q1.
conclusionConstitutively active I(Q1E1) and a smaller peak I(Q1E1) are common features of FAF-associated and LQT1-associated mutations, respectively. These data suggest that the mixed functional properties of R231C-Q1 may predispose some families to LQT1 or FAF. We conclude that R231C is a pleiotropic missense mutation capable of LQT1 expression, AF expression, or both.
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