Haploinsufficiency of vascular endothelial growth factor related signaling genes is associated with tetralogy of Fallot
| Autor: | Anne S. Bassett, Meredith Curtis, Gregory Costain, Miriam S. Reuter, Stephen W. Scherer, Chelsea Lowther, Rebekah Jobling, Christian R. Marshall, Candice K. Silversides, Erwin Oechslin, Raymond H. Kim, Heinrich Sticht, Bhooma Thiruvahindrapuram, Rajiv Chaturvedi, Susan Walker, S. Mohsen Hosseini, Roozbeh Manshaei, Spencer van Mil, Tracy Heung, Rachel M. Wald, Eriskay Liston |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Proband Adult Male Vascular Endothelial Growth Factor A Haploinsufficiency 030105 genetics & heredity Biology Brief Communication Pathogenesis 03 medical and health sciences chemistry.chemical_compound Loss of Function Mutation Conotruncal defect medicine Humans Genetic Predisposition to Disease FLT4 Genetics (clinical) Genetic Association Studies Tetralogy of Fallot Aged Genetics Whole Genome Sequencing conotruncal defects Middle Aged medicine.disease Vascular Endothelial Growth Factor Receptor-3 VEGF congenital heart disease Vascular Endothelial Growth Factor Receptor-2 3. Good health Vascular endothelial growth factor genome sequencing Vascular endothelial growth factor A 030104 developmental biology chemistry Female Signal Transduction |
| Zdroj: | Genetics in Medicine |
| ISSN: | 1530-0366 1098-3600 |
| Popis: | Purpose To determine disease-associated single-gene variants in conotruncal defects, particularly tetralogy of Fallot (TOF). Methods We 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. Results We 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 |
| Databáze: | OpenAIRE |
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