Rare variants in KDR, encoding VEGF Receptor 2, are associated with tetralogy of Fallot.

ABSTRACT:

Purpose

Rare 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.

Methods

We 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.

Results

Exome 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,

SUBMITTER: Skoric-Milosavljevic D 

PROVIDER: S-EPMC8486653 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature