ArticleCirculation research2019
Whole Exome Sequencing Reveals the Major Genetic Contributors to Nonsyndromic Tetralogy of Fallot.
Article in Circulation research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 4 of them syntheses that pooled it.
What it found
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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
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Who cites it
121 citing papers in PubMed, 4 syntheses or guidelines pooled it, 193 citations in OpenAlex.
- Single-cell reconstruction and mutation enrichment analysis identifies dysregulated cardiomyocyte and endothelial cells in congenital heart disease.Physiological genomics · 2023Pooled it
- Contribution of NOTCH1 genetic variants to bicuspid aortic valve and other congenital lesions.Heart (British Cardiac Society) · 2022Pooled it
- Germline variants in HEY2 functional domains lead to congenital heart defects and thoracic aortic aneurysms.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Pooled it
- Integration of Large-Scale Genomic Data Sources With Evolutionary History Reveals Novel Genetic Loci for Congenital Heart Disease.Circulation. Genomic and precision medicine · 2019Pooled it
- Clinical Genetic Risk Variants Inform a Functional Protein Interaction Network for Tetralogy of Fallot.Circulation. Genomic and precision medicine · 2021Trial
- Congenital heart disease risk loci identified by genome-wide association study in European patients.The Journal of clinical investigation · 2021Trial
- Article
- Diagnostic Yield of Exome Sequencing in Patients With Congenital Heart Disease From Southern Africa.Circulation. Genomic and precision medicine · 2026Article
- Functional noncoding variants within the TBX1 enhancer contribute to tetralogy of Fallot.Science China. Life sciences · 2026Article
- Single-cell omics uncovers novel pathological mechanisms and therapeutic targets for congenital heart diseases: insights from integrated intercellular communication analysis.Stem cell research & therapy · 2026Review
- Non-isolated tetralogy of fallot (TOF+): exome sequencing efficacy and phenotypic expansions.European journal of human genetics : EJHG · 2026Article
- Review
- DNA methylation analysis of NOTCH1 variants reveals the first episignature for non-syndromic congenital heart defects.Genome medicine · 2026Article
- Article
- Modelling Tetralogy of Fallot: insights and limitations of animal models.Frontiers in cell and developmental biology · 2026Review
- Identification of a NovelDiagnostics (Basel, Switzerland) · 2025Article
- Circulating Cardiovascular Proteomic Associations With Genetics and Disease.Circulation. Genomic and precision medicine · 2025Article
- Deep learning the dynamic regulatory sequence code of cardiac organoid differentiation.bioRxiv : the preprint server for biology · 2025Article
- Loss-of-function variants in ciliary genes confer high risk for tetralogy of Fallot.Science advances · 2025Article
- Genetics of Congenital Heart Disease: A Narrative Review of Challenges and Strategies in Identifying Novel Genes.Cureus · 2025Review
61 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
34 authors at 11 institutions in 6 countries.
Funding
Abstract
rationaleFamilial recurrence studies provide strong evidence for a genetic component to the predisposition to sporadic, nonsyndromic Tetralogy of Fallot (TOF), the most common cyanotic congenital heart disease phenotype. Rare genetic variants have been identified as important contributors to the risk of congenital heart disease, but relatively small numbers of TOF cases have been studied to date.
objectiveWe used whole exome sequencing to assess the prevalence of unique, deleterious variants in the largest cohort of nonsyndromic TOF patients reported to date. METHODS AND
resultsEight hundred twenty-nine TOF patients underwent whole exome sequencing. The presence of unique, deleterious variants was determined; defined by their absence in the Genome Aggregation Database and a scaled combined annotation-dependent depletion score of ≥20. The clustering of variants in 2 genes, NOTCH1 and FLT4, surpassed thresholds for genome-wide significance (assigned as P<5×10
conclusionsThe NOTCH1 locus is the most frequent site of genetic variants predisposing to nonsyndromic TOF, followed by FLT4. Together, variants in these genes are found in almost 7% of TOF patients.
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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.