ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm.

ABSTRACT: Bicuspid aortic valve (BAV) is a common congenital heart defect (population incidence, 1-2%)^1-3 that frequently presents with ascending aortic aneurysm (AscAA)⁴. BAV/AscAA shows autosomal dominant inheritance with incomplete penetrance and male predominance. Causative gene mutations (for example, NOTCH1, SMAD6) are known for ≤1% of nonsyndromic BAV cases with and without AscAA^5-8, impeding mechanistic insight and development of therapeutic strategies. Here, we report the identification of variants in ROBO4 (which encodes a factor known to contribute to endothelial performance) that segregate with disease in two families. Targeted sequencing of ROBO4 showed enrichment for rare variants in BAV/AscAA probands compared with controls. Targeted silencing of ROBO4

SUBMITTER: Gould RA 

PROVIDER: S-EPMC6309588 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature