ArticleCirculation research2013
An in vivo cardiac assay to determine the functional consequences of putative long QT syndrome mutations.
Article in Circulation research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 38 citations in OpenAlex.
- Torsades de Pointes electrical storm in children with KCNH2 mutations.BMC medical genomics · 2024Article
- Zebrafish cardiac repolarization does not functionally depend on the expression of the hERG1b-like transcript.Pflugers Archiv : European journal of physiology · 2024Article
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- 1029 genomes of self-declared healthy individuals from India reveal prevalent and clinically relevant cardiac ion channelopathy variants.Human genomics · 2022Article
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- How Functional Genomics Can Keep Pace With VUS Identification.Frontiers in cardiovascular medicine · 2022Review
- Cardioluminescence in Transgenic Zebrafish Larvae: A Calcium Imaging Tool to Study Drug Effects and Pathological Modeling.Biomedicines · 2021Article
- Zebrafish, an In Vivo Platform to Screen Drugs and Proteins for Biomedical Use.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Myocyte-specific enhancer factor 2c triggers transdifferentiation of adipose tissue-derived stromal cells into spontaneously beating cardiomyocyte-like cells.Scientific reports · 2021Article
- Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases.Cardiovascular research · 2020Article
- Reclassification of genetic variants in children with long QT syndrome.Molecular genetics & genomic medicine · 2020Article
- Automated high-throughput heartbeat quantification in medaka and zebrafish embryos under physiological conditions.Scientific reports · 2020Article
- Adult and Developing Zebrafish as Suitable Models for Cardiac Electrophysiology and Pathology in Research and Industry.Frontiers in physiology · 2020Review
- Utility of Zebrafish Models of Acquired and Inherited Long QT Syndrome.Frontiers in physiology · 2020Review
- Investigating the utility of adult zebrafish ex vivo whole hearts to pharmacologically screen hERG channel activator compounds.American journal of physiology. Regulatory, integrative and comparative physiology · 2019Article
- Functional analysis of KCNH2 gene mutations of type 2 long QT syndrome in larval zebrafish using microscopy and electrocardiography.Heart and vessels · 2019Article
- Rescue of protein expression defects may not be enough to abolish the pro-arrhythmic phenotype of long QT type 2 mutations.The Journal of physiology · 2016Article
- Precise Editing of the Zebrafish Genome Made Simple and Efficient.Developmental cell · 2016Article
- New approaches to establish genetic causality.Trends in cardiovascular medicine · 2015Review
- New and TALENted genome engineering toolbox.Circulation research · 2013Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
rationaleGenetic testing for Long QT Syndrome is now a standard and integral component of clinical cardiology. A major obstacle to the interpretation of genetic findings is the lack of robust functional assays to determine the pathogenicity of identified gene variants in a high-throughput manner.
objectiveThe goal of this study was to design and test a high-throughput in vivo cardiac assay to distinguish between disease-causing and benign KCNH2 (hERG1) variants, using the zebrafish as a model organism. METHODS AND
resultsWe tested the ability of previously characterized Long QT Syndrome hERG1 mutations and polymorphisms to restore normal repolarization in the kcnh2-knockdown embryonic zebrafish. The cardiac assay correctly identified a benign variant in 9 of 10 cases (negative predictive value 90%), whereas correctly identifying a disease-causing variant in 39/39 cases (positive predictive value 100%).
conclusionsThe in vivo zebrafish cardiac assay approaches the accuracy of the current benchmark in vitro assay for the detection of disease-causing mutations, and is far superior in terms of throughput rate. Together with emerging algorithms for interpreting a positive long QT syndrome genetic test, the zebrafish cardiac assay provides an additional tool for the final determination of pathogenicity of gene variants identified in long QT syndrome genetic screening.
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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.