ArticleThe Journal of clinical investigation2008
The E1784K mutation in SCN5A is associated with mixed clinical phenotype of type 3 long QT syndrome.
Article in The Journal of clinical investigation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 1 of them a synthesis that pooled it.
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Who cites it
90 citing papers in PubMed, 1 synthesis or guideline pooled it, 235 citations in OpenAlex.
- Variability in reported midpoints of (in)activation of cardiac INa.The Journal of general physiology · 2025Pooled it
- A bifunctional actuator to correct loss-of-function deficits in cardiac voltage-gated sodium channels.Science advances · 2026Article
- Sex-specific virtual population for the prediction and assessment of arrhythmia risk.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
- Ventricular conduction is a marker for arrhythmic risk in SCN5A-E1784K overlap sodium channel disease.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 · 2026Observational
- Clinical Spectrum of Arrhythmogenic Entities in Spanish Children Carrying DeleteriousInternational journal of molecular sciences · 2026Article
- Identification of Two Rare Variants in Iranian Families With Familial Sudden Cardiac Death.International journal of genomics · 2026Article
- Multiscale computational analysis reveals enhanced allosteric modulation of Nav1.5 by dual binding of dapagliflozin and ertugliflozin.Scientific reports · 2025Article
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- A Novel Bradycardia-Associated Variant inBiomedicines · 2025Article
- Exploring epicardial arrhythmogenic substrates in long QT syndrome type III overlapping with J-wave syndrome.HeartRhythm case reports · 2025Article
- Multisite Validation of a Functional Assay to AdjudicateCirculation. Genomic and precision medicine · 2024Article
- Biophysical mechanisms of myocardium sodium channelopathies.Pflugers Archiv : European journal of physiology · 2024Review
- Human Genetics of Cardiac Arrhythmias.Advances in experimental medicine and biology · 2024Review
- Multi-site validation of a functional assay to adjudicatemedRxiv : the preprint server for health sciences · 2023Article
- Current gaps in knowledge in inherited arrhythmia syndromes.Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation · 2023Review
- Precision medicine for long QT syndrome: patient-specific iPSCs take the lead.Expert reviews in molecular medicine · 2023Review
- Development of automated patch clamp assays to overcome the burden of variants of uncertain significance in inheritable arrhythmia syndromes.Frontiers in physiology · 2023Review
- Exploring mutation specific beta blocker pharmacology of the pathogenic late sodium channel current from patient-specific pluripotent stem cell myocytes derived from long QT syndrome mutation carriers.Channels (Austin, Tex.) · 2022Article
- European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases.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 · 2022Article
- European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases.Journal of arrhythmia · 2022Article
30 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 11 institutions in 6 countries.
Funding
Abstract
Phenotypic overlap of type 3 long QT syndrome (LQT3) with Brugada syndrome (BrS) is observed in some carriers of mutations in the Na channel SCN5A. While this overlap is important for patient management, the clinical features, prevalence, and mechanisms underlying such overlap have not been fully elucidated. To investigate the basis for this overlap, we genotyped a cohort of 44 LQT3 families of multiple ethnicities from 7 referral centers and found a high prevalence of the E1784K mutation in SCN5A. Of 41 E1784K carriers, 93% had LQT3, 22% had BrS, and 39% had sinus node dysfunction. Heterologously expressed E1784K channels showed a 15.0-mV negative shift in the voltage dependence of Na channel inactivation and a 7.5-fold increase in flecainide affinity for resting-state channels, properties also seen with other LQT3 mutations associated with a mixed clinical phenotype. Furthermore, these properties were absent in Na channels harboring the T1304M mutation, which is associated with LQT3 without a mixed clinical phenotype. These results suggest that a negative shift of steady-state Na channel inactivation and enhanced tonic block by class IC drugs represent common biophysical mechanisms underlying the phenotypic overlap of LQT3 and BrS and further indicate that class IC drugs should be avoided in patients with Na channels displaying these behaviors.
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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.