The (patho)genetic study of bicuspid aortic valve and associated aortic aneurysm

Bicuspid aortic valve (BAV), a heart valve with only two leaflets instead of three, is the most common congenital heart defect with an estimated prevalence of approximately 1-2%. The heart defect often remains asymptomatic but ascending aortic aneurysms develop in 10-20% of the bicuspid aortic valve patients. If not detected in a timely fashion, this can lead to aortic dissection with an important mortality. Due to the prevalent nature of this heart defect, bicuspid aortic valve disease presents an important health problem. Historically, it was hypothesized that abnormal blood flow across the bicuspid aortic valve led to aneurysm formation. However in recent years, an important genetic contribution has been suggested and it is currently believed that the same genetic factors predispose to the developmental valve defect and the aortic aneurysm formation. The inheritance pattern is most nsistent with an autosomal dominant disorder with variable penetrance and expressivity.Within this project, two specific aims will be pursued. Firstly, we will investigate the potentialcontribution of canonical and non-canonical TGFβ signaling cascades in BAV that have beenfirmly implicated in Marfan-related aneurysms. Secondly, we will identify the genetic basisusing a state-of-the-art technique: whole exome sequencing.

Keywords:HEREDITARY, ANEURYSMS

Disciplines:Genetics, Systems biology, Laboratory medicine, Molecular and cell biology, Palliative care and end-of-life care, Regenerative medicine, Other basic sciences, Other clinical sciences, Other health sciences, Nursing, Other paramedical sciences, Other translational sciences, Other medical and health sciences