ArticleHeart rhythm2016
Stop-codon and C-terminal nonsense mutations are associated with a lower risk of cardiac events in patients with long QT syndrome type 1.
Article in Heart rhythm, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Software-based analysis of T-wave morphology: identifying the electrocardiogram signature of high-risk long QT syndrome.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 · 2025Article
- Role of Cardiovascular Magnetic Resonance in the Management of Atrial Fibrillation: A Review.Journal of imaging · 2022Review
- Eosinophilic Infiltration of the Sino-Atrial Node in Sudden Cardiac Death Caused by Long QT Syndrome.International journal of molecular sciences · 2022Article
- Membrane pools of phosphatidylinositol-4-phosphate regulate KCNQ1/KCNE1 membrane expression.Communications biology · 2021Article
- Atrial fibrillation and atrial cardiomyopathies.Journal of cardiovascular electrophysiology · 2021Review
- A cryptic splice-altering KCNQ1 variant in trans with R259L leading to Jervell and Lange-Nielsen syndrome.NPJ genomic medicine · 2021Article
- A novel mutation KCNQ1p.Thr312del is responsible for long QT syndrome type 1.Heart and vessels · 2019Article
- Genetic Testing for Inherited Cardiac Arrhythmias: Current State-of-the-Art and Future Avenues.The Journal of innovations in cardiac rhythm management · 2018Review
- From Genotype to Phenotype.Circulation. Genomic and precision medicine · 2018Review
- The genetic architecture of long QT syndrome: A critical reappraisal.Trends in cardiovascular medicine · 2018Review
- Genetic and Phenotypic Characterization of Community Hospital Patients With QT Prolongation.Journal of the American Heart Association · 2018Article
- Molecular Pathophysiology of Congenital Long QT Syndrome.Physiological reviews · 2017Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundIn long QT syndrome type 1 (LQT1), the location and type of mutations have been shown to affect the clinical outcome. Although haploinsufficiency, including stop-codon and frameshift mutations, has been associated with a lower risk of cardiac events in patients with LQT1, nonsense mutations have been presumed functionally equivalent.
objectiveThe purpose of this study was to evaluate clinical differences between patients with nonsense mutations.
methodsThe study sample comprised 1090 patients with genetically confirmed mutations. Patients were categorized into 5 groups, depending on mutation type and location: missense not located in the high-risk cytoplasmic loop (c-loop) (n = 698), which is used as reference; missense c-loop (n = 192); stop-codon (n = 67); frameshift (n = 39); and others (n = 94). The primary outcome was a composite end point of syncope, aborted cardiac arrest, and long QT syndrome-related death (cardiac events). Outcomes were evaluated using the multivariate Cox proportional hazards regression analysis. Standard patch clamp techniques were used.
resultsCompared to patients with missense non-c-loop mutations, the risk of cardiac events was reduced significantly in patients with stop-codon mutations (hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.34-0.96; P = .035), but not in patients with frameshift mutations (HR 1.01; 95% CI 0.58-1.77; P = .97). Our data suggest that currents of the most common stop-codon mutant channel (Q530X) were larger than those of haploinsufficient channels (wild type: 42 ± 6 pA/pF, n = 20; Q530X+wild type: 79 ± 14 pA/pF, n = 20; P < .05) and voltage dependence of activation was altered.
conclusionStop-codon mutations are associated with a lower risk of cardiac events in patients with LQT1, while frameshift mutations are associated with the same risk as the majority of the missense mutations. Our data indicate functional differences between these previously considered equivalent mutation subtypes.
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