Evidence map›Paper›PMID 27157848›Full record

ArticleHeart rhythm2016

A novel heterozygous mutation in cardiac calsequestrin causes autosomal dominant catecholaminergic polymorphic ventricular tachycardia.

Belinda Gray, Richard D Bagnall, Lien Lam, Jodie Ingles, Christian Turner, Eric Haan, Andrew Davis, Pei-Chi Yang, Colleen E Clancy, Raymond W Sy and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

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 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
5.4field-weighted citation impact, top 4% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 72 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Review
  5. Cardiac Channelopathies: Clinical Diagnosis and Promising Therapeutics.Journal of the American Heart Association · 2025
    Review
  6. Article
  7. Human Genetics of Cardiac Arrhythmias.Advances in experimental medicine and biology · 2024
    Review
  8. Article
  9. Review
  10. Review
  11. Role of CaArchives of toxicology · 2023
    Review
  12. Article
  13. 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 · 2022
    Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. Calsequestrin, a key protein in striated muscle health and disease.Journal of muscle research and cell motility · 2021
    Review
  20. Life-threatening arrhythmias with autosomal recessive TECRL variants.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 · 2021
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 7 institutions in 2 countries.

Belinda GrayDepartment of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, New South Wales, Australia.
Richard D BagnallSydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, New South Wales, Australia.
Lien LamSydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, New South Wales, Australia.
Jodie InglesDepartment of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, New South Wales, Australia.
Christian TurnerDepartment of Cardiology, Westmead Children's Hospital, Sydney, New South Wales, Australia.
Eric HaanAdult Genetics Unit, South Australian Clinical Genetics Service, SA Pathology and School of Medicine, University of Adelaide, Adelaide, New South Wales, Australia.
Andrew DavisDepartment of Cardiology, The Royal Children's Hospital Melbourne, Melbourne, New South Wales, Victoria, Australia.
Pei-Chi YangDepartment of Pharmacology, University of California, Davis, California, USA.
Colleen E ClancyDepartment of Pharmacology, University of California, Davis, California, USA.
Raymond W SyDepartment of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Christopher SemsarianDepartment of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia; Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, New South Wales, Australia. Electronic address: c.semsarian@centenary.org.au.
University of Sydney · AUCentenary Institute · AUUniversity of California, Davis · USChildren's Hospital at Westmead · AURoyal Children's Hospital · AURoyal Prince Alfred Hospital · AUUniversity of Adelaide · AU

Funding

In silico Safety PharmacologyR01HL128537 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI CLANCY, COLLEEN E, SANTANA, LUIS F · 2016 to 2024
$5.7M
Predictive multiscale in silico cardio-pharmacologyU01HL126273 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI CLANCY, COLLEEN E · 2015 to 2019
$3.8M
A Systems Biology Approach to Study Cardiac Arrhythmias: iPS Cells and In Silico ModelingR01HL128170 · NHLBI · STANFORD UNIVERSITY · PI ALTMAN, RUSS BIAGIO, CLANCY, COLLEEN E · 2015 to 2018
$3.0M
NHLBI NIH HHS R01 HL128170NHLBI NIH HHS R01 HL128537NHLBI NIH HHS U01 HL126273
6 · The paper itself

Abstract

backgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal inherited arrhythmia syndrome characterized by adrenergically stimulated ventricular tachycardia. Mutations in the cardiac ryanodine receptor gene (RYR2) cause an autosomal dominant form of CPVT, while mutations in the cardiac calsequestrin 2 gene (CASQ2) cause an autosomal recessive form.

objectiveThe aim of this study was to clinically and genetically evaluate a large family with severe autosomal dominant CPVT.

methodsClinical evaluation of family members was performed, including detailed history, physical examination, electrocardiogram, exercise stress test, and autopsy review of decedents. We performed genome-wide linkage analysis in 12 family members and exome sequencing in 2 affected family members. In silico models of mouse and rabbit myocyte electrophysiology were used to predict potential disease mechanisms.

resultsSevere CPVT with dominant inheritance in 6 members was diagnosed in a large family with 2 sudden deaths, 2 resuscitated cardiac arrests, and multiple appropriate implantable cardioverter-defibrillator shocks. A comprehensive analysis of cardiac arrhythmia genes did not reveal a pathogenic variant. Exome sequencing identified a novel heterozygous missense variant in CASQ2 (Lys180Arg) affecting a highly conserved residue, which cosegregated with disease and was absent in unaffected family members. Genome-wide linkage analysis confirmed a single linkage peak at the CASQ2 locus (logarithm of odds ratio score 3.01; θ = 0). Computer simulations predicted that haploinsufficiency was unlikely to cause the severe CPVT phenotype and suggested a dominant negative mechanism.

conclusionWe show for the first time that a variant in CASQ2 causes autosomal dominant CPVT. Genetic testing in dominant CPVT should include screening for heterozygous CASQ2 variants.

Indexed as

MutationAdolescentAdultAgedAged, 80 and overAnimalsCalsequestrinChildChild, PreschoolDNADNA Mutational AnalysisElectrocardiographyFemaleGenetic TestingHeterozygoteHumansCalsequestrinCASQ2 protein, humanDNARyanodine Receptor Calcium Release ChannelAutosomal dominantCardiac calsequestrinCPVTHeterozygous

Identifiers

PMID27157848
PMCPMC5453511
OpenAlexW2345850685

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.