ArticleGenetics in medicine : official journal of the American College of Medical Genetics2019
Haploinsufficiency of vascular endothelial growth factor related signaling genes is associated with tetralogy of Fallot.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Genome-wide association studies highlight novel risk loci for septal defects and left-sided congenital heart defects.BMC genomics · 2024Pooled it
- Clinical Genetic Risk Variants Inform a Functional Protein Interaction Network for Tetralogy of Fallot.Circulation. Genomic and precision medicine · 2021Trial
- Article
- Assessing the contribution of rare variants to congenital heart disease through a large-scale case-control exome study.NPJ genomic medicine · 2026Article
- Review
- Decreased Kinase Activity of the VEGFR3 Variant c.3175G>C Associated with Primary Lymphedema.Current issues in molecular biology · 2026Article
- Refractory Peripheral Pulmonary Stenosis and Severe Pulmonary Arterial Hypertension Associated With aPulmonary circulation · 2026Article
- Loss-of-function variants in ciliary genes confer high risk for tetralogy of Fallot.Science advances · 2025Article
- Genetics of Congenital Heart Disease.Clinics in perinatology · 2025Review
- RNA-sequencing unveils FLT4 splice site variants in variable congenital heart disease.European journal of human genetics : EJHG · 2025Article
- Developmental and Evolutionary Heart Adaptations Through Structure-Function Relationships.Journal of cardiovascular development and disease · 2025Review
- Case Report: a novel missense variant ofFrontiers in genetics · 2025Article
- Article
- FLT4 causes developmental disorders of the cardiovascular and lymphovascular systems via pleiotropic molecular mechanisms.Cardiovascular research · 2024Article
- FLT4 gene polymorphisms influence isolated ventricular septal defect predisposition in a Southwest China population.BMC medical genomics · 2024Article
- Investigation of coagulation and proteomics profiles in symptomatic feline hypertrophic cardiomyopathy and healthy control cats.BMC veterinary research · 2024Article
- Association study of FLT4 and HYDIN single nucleotide polymorphisms with atrial septal defect susceptibility in the Han Chinese population of Southwest China.Italian journal of pediatrics · 2024Article
- In-Depth Genomic Analysis: The New Challenge in Congenital Heart Disease.International journal of molecular sciences · 2024Review
- Review
- Clinically Relevant Genetic Considerations for Patients With Tetralogy of Fallot.CJC pediatric and congenital heart disease · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 7 institutions in 2 countries.
Funding
Abstract
purposeTo determine disease-associated single-gene variants in conotruncal defects, particularly tetralogy of Fallot (TOF).
methodsWe analyzed for rare loss-of-function and deleterious variants in FLT4 (VEGFR3) and other genes in the vascular endothelial growth factor (VEGF) pathway, as part of a genome sequencing study involving 175 adults with TOF from a single site.
resultsWe identified nine (5.1%) probands with novel FLT4 variants: seven loss-of-function, including an 8-kb deletion, and two predicted damaging. In ten other probands we found likely disruptive variants in VEGF-related genes: KDR (VEGFR2; two stopgain and two nonsynonymous variants), VEGFA, FGD5, BCAR1, IQGAP1, FOXO1, and PRDM1. Detection of VEGF-related variants (19/175, 10.9%) was associated with an increased prevalence of absent pulmonary valve (26.3% vs. 3.4%, p < 0.0001) and right aortic arch (52.6% vs. 29.1%, p = 0.029). Extracardiac anomalies were rare. In an attempt to replicate findings, we identified three loss-of-function or damaging variants in FLT4, KDR, and IQGAP1 in ten independent families with TOF.
conclusionLoss-of-function variants in FLT4 and KDR contribute substantially to the genetic basis of TOF. The findings support dysregulated VEGF signaling as a novel mechanism contributing to the pathogenesis of TOF.
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.