Haploinsufficiency of vascular endothelial growth factor related signaling genes is associated with tetralogy of Fallot.

ABSTRACT: 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?

SUBMITTER: Reuter MS 

PROVIDER: S-EPMC6752294 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature