ArticleProceedings of the National Academy of Sciences of the United States of America2013
KCNJ2 mutation in short QT syndrome 3 results in atrial fibrillation and ventricular proarrhythmia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 146 citations in OpenAlex.
- Repurposing polyamines to prevent life-threatening arrhythmias in Short QT Syndrome type 3.Nature communications · 2026Article
- Identification of a Novel Genetic Variant Responsible for Familial Atrial Fibrillation.The Canadian journal of cardiology · 2026Article
- A Novel KCNJ2 p.Glu299Ala Variant Associated with Short QT Phenotype and Persistent Atrial Fibrillation in a Child.Life (Basel, Switzerland) · 2026Article
- A new approach methodology for studying intrinsic ventricular arrhythmias in Fabry disease.Frontiers in cardiovascular medicine · 2026Article
- Biphasic effects on human atrial arrhythmogenicity of L-type calcium channel mutations associated with a Brugada/Short QT overlap syndrome - insights from a multiscale simulation study.PLoS computational biology · 2025Article
- Ventricular ion channels and arrhythmias: an overview of physiology, pathophysiology and pharmacology.Medical review (2021) · 2025Review
- The Uncommon Phenomenon of Short QT Syndrome: A Scoping Review of the Literature.Journal of personalized medicine · 2025Review
- Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.Cell discovery · 2025Review
- Alleviating the Effects of Short QT Syndrome Type 3 by Allele-Specific Suppression of theInternational journal of molecular sciences · 2024Article
- Interpreting the actionable clinical role of rare variants associated with short QT syndrome.Human genetics · 2024Article
- Identification of the optimal reference genes for atrial fibrillation model established by iPSC-derived atrial myocytes.BMC genomics · 2024Article
- The network of cardiac KNaunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Atrial fibrillation in the young: consider heritable conditions like short QT syndrome.Cardiovascular research · 2024Article
- The Kir2.1E299V mutation increases atrial fibrillation vulnerability while protecting the ventricles against arrhythmias in a mouse model of short QT syndrome type 3.Cardiovascular research · 2024Article
- Impact of rs1805127 and rs55742440 Variants on Atrial Remodeling in Hypertrophic Cardiomyopathy Patients with Atrial Fibrillation: A Romanian Cohort Study.International journal of molecular sciences · 2023Article
- Pro-arrhythmic effects of gain-of-function potassium channel mutations in the short QT syndrome.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Molecular stratification of arrhythmogenic mechanisms in the Andersen Tawil syndrome.Cardiovascular research · 2023Article
- Verification of the Efficacy of Mexiletine Treatment for the A1656D Mutation on Downgrading Reentrant Tachycardia Using a 3D Cardiac Electrophysiological Model.Bioengineering (Basel, Switzerland) · 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
- Inward rectifier potassium (Kir) channels in the retina: living our vision.American journal of physiology. Cell physiology · 2022Review
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
We describe a mutation (E299V) in KCNJ2, the gene that encodes the strong inward rectifier K(+) channel protein (Kir2.1), in an 11-y-old boy. The unique short QT syndrome type-3 phenotype is associated with an extremely abbreviated QT interval (200 ms) on ECG and paroxysmal atrial fibrillation. Genetic screening identified an A896T substitution in a highly conserved region of KCNJ2 that resulted in a de novo mutation E299V. Whole-cell patch-clamp experiments showed that E299V presents an abnormally large outward IK1 at potentials above -55 mV (P < 0.001 versus wild type) due to a lack of inward rectification. Coexpression of wild-type and mutant channels to mimic the heterozygous condition still resulted in a large outward current. Coimmunoprecipitation and kinetic analysis showed that E299V and wild-type isoforms may heteromerize and that their interaction impairs function. The homomeric assembly of E299V mutant proteins actually results in gain of function. Computer simulations of ventricular excitation and propagation using both the homozygous and heterozygous conditions at three different levels of integration (single cell, 2D, and 3D) accurately reproduced the electrocardiographic phenotype of the proband, including an exceedingly short QT interval with merging of the QRS and the T wave, absence of ST segment, and peaked T waves. Numerical experiments predict that, in addition to the short QT interval, absence of inward rectification in the E299V mutation should result in atrial fibrillation. In addition, as predicted by simulations using a geometrically accurate three-dimensional ventricular model that included the His-Purkinje network, a slight reduction in ventricular excitability via 20% reduction of the sodium current should increase vulnerability to life-threatening ventricular tachyarrhythmia.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.