ArticleHeart rhythm2016
Novel calmodulin mutations associated with congenital long QT syndrome affect calcium current in human cardiomyocytes.
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 32 papers, 1 of them a synthesis that pooled it.
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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- An International, Multicentered, Evidence-Based Reappraisal of Genes Reported to Cause Congenital Long QT Syndrome.Circulation · 2020Pooled it
- Assessment of paralogue annotation for improving diagnostic accuracy inFrontiers in genetics · 2026Article
- Calmodulin D133H Disrupts CaCells · 2025Article
- The mechanism of LQTS related CaM mutation E141G interfering with CaJournal of physiology and biochemistry · 2025Article
- Arrhythmogenic calmodulin variants D131E and Q135P disrupt interaction with the L-type voltage-gated CaActa physiologica (Oxford, England) · 2025Article
- Cardiac conduction diseases: understanding the molecular mechanisms to uncover targets for future treatments.Expert opinion on therapeutic targets · 2024Review
- Calmodulin Mutations in Human Disease.Channels (Austin, Tex.) · 2023Review
- Arrhythmia-associated calmodulin variants interact with KCNQ1 to confer aberrant membrane trafficking and function.PNAS nexus · 2023Article
- Sex and Gene Influence Arrhythmia Susceptibility in Murine Models of Calmodulinopathy.Circulation. Arrhythmia and electrophysiology · 2023Article
- Long QT syndrome-associated calmodulin variants disrupt the activity of the slowly activating delayed rectifier potassium channel.The Journal of physiology · 2023Article
- Calcium Signalling in Heart and Vessels: Role of Calmodulin and Downstream Calmodulin-Dependent Protein Kinases.International journal of molecular sciences · 2022Review
- Alterations in calmodulin-cardiac ryanodine receptor molecular recognition in congenital arrhythmias.Cellular and molecular life sciences : CMLS · 2022Article
- Case report: Prenatal diagnosis of fetal non-compaction cardiomyopathy with bradycardia accompanied byFrontiers in pediatrics · 2022Article
- Long QT syndrome - Bench to bedside.Heart rhythm O2 · 2021Article
- Predicting Genetic Variation Severity Using Machine Learning to Interpret Molecular Simulations.Biophysical journal · 2021Article
- Article
- Regulation of cardiovascular calcium channel activity by post-translational modifications or interacting proteins.Pflugers Archiv : European journal of physiology · 2020Review
- Calmodulin Mutations Associated with Heart Arrhythmia: A Status Report.International journal of molecular sciences · 2020Review
- Impact of arrhythmogenic calmodulin variants on small conductance CaPhysiological reports · 2019Article
- Calmodulin mutations and life-threatening cardiac arrhythmias: insights from the International Calmodulinopathy Registry.European heart journal · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundCalmodulin (CaM) mutations are associated with cardiac arrhythmia susceptibility including congenital long QT syndrome (LQTS).
objectiveThe purpose of this study was to determine the clinical, genetic, and functional features of 2 novel CaM mutations in children with life-threatening ventricular arrhythmias.
methodsThe clinical and genetic features of 2 congenital arrhythmia cases associated with 2 novel CaM gene mutations were ascertained. Biochemical and functional investigations were conducted on the 2 mutations.
resultsA novel de novo CALM2 mutation (D132H) was discovered by candidate gene screening in a male infant with prenatal bradycardia born to healthy parents. Postnatal course was complicated by profound bradycardia, prolonged corrected QT interval (651 ms), 2:1 atrioventricular block, and cardiogenic shock. He was resuscitated and was treated with a cardiac device. A second novel de novo mutation in CALM1 (D132V) was discovered by clinical exome sequencing in a 3-year-old boy who suffered a witnessed cardiac arrest secondary to ventricular fibrillation. Electrocardiographic recording after successful resuscitation revealed a prolonged corrected QT interval of 574 ms. The Ca(2+) affinity of CaM-D132H and CaM-D132V revealed extremely weak binding to the C-terminal domain, with significant structural perturbations noted for D132H. Voltage-clamp recordings of human induced pluripotent stem cell-derived cardiomyocytes transiently expressing wild-type or mutant CaM demonstrated that both mutations caused impaired Ca(2+)-dependent inactivation of voltage-gated Ca(2+) current. Neither mutant affected voltage-dependent inactivation.
conclusionOur findings implicate impaired Ca(2+)-dependent inactivation in human cardiomyocytes as the plausible mechanism for long QT syndrome associated with 2 novel CaM mutations. The data further expand the spectrum of genotype and phenotype associated with calmodulinopathy.
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.