ArticleGenetics in medicine : official journal of the American College of Medical Genetics2021
Rare variants in KDR, encoding VEGF Receptor 2, are associated with tetralogy of Fallot.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
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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.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Refractory Peripheral Pulmonary Stenosis and Severe Pulmonary Arterial Hypertension Associated With aPulmonary circulation · 2026Article
- 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
- A novel mutation inGenes & diseases · 2025Article
- Why some and not others? Understanding vascular phenotypes in genetic developmental lung diseases.Current opinion in pediatrics · 2025Review
- In-Depth Genomic Analysis: The New Challenge in Congenital Heart Disease.International journal of molecular sciences · 2024Review
- Genome Sequencing of Idiopathic Speech Delay.Human mutation · 2024Article
- Clinically Relevant Genetic Considerations for Patients With Tetralogy of Fallot.CJC pediatric and congenital heart disease · 2023Review
- Biological and structural phenotypes associated with neurodevelopmental outcomes in congenital heart disease.Translational pediatrics · 2023Review
- Genetic insights into non-syndromic Tetralogy of Fallot.Frontiers in physiology · 2022Review
- Case Report: Tetralogy of Fallot in a Chinese Family Caused by a Novel Missense Variant ofFrontiers in cardiovascular medicine · 2022Article
- Genetics of congenital heart disease: a narrative review of recent advances and clinical implications.Translational pediatrics · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
49 authors at 20 institutions in 8 countries.
Funding
Abstract
purposeRare genetic variants in KDR, encoding the vascular endothelial growth factor receptor 2 (VEGFR2), have been reported in patients with tetralogy of Fallot (TOF). However, their role in disease causality and pathogenesis remains unclear.
methodsWe conducted exome sequencing in a familial case of TOF and large-scale genetic studies, including burden testing, in >1,500 patients with TOF. We studied gene-targeted mice and conducted cell-based assays to explore the role of KDR genetic variation in the etiology of TOF.
resultsExome sequencing in a family with two siblings affected by TOF revealed biallelic missense variants in KDR. Studies in knock-in mice and in HEK 293T cells identified embryonic lethality for one variant when occurring in the homozygous state, and a significantly reduced VEGFR2 phosphorylation for both variants. Rare variant burden analysis conducted in a set of 1,569 patients of European descent with TOF identified a 46-fold enrichment of protein-truncating variants (PTVs) in TOF cases compared to controls (P = 7 × 10
conclusionRare KDR variants, in particular PTVs, strongly associate with TOF, likely in the setting of different inheritance patterns. Supported by genetic and in vivo and in vitro functional analysis, we propose loss-of-function of VEGFR2 as one of the mechanisms involved in the pathogenesis of TOF.
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