Bicuspid Aortic Valves (BAV) can cause premature deaths due to aortic stenosis, aortic regurgitation or Thoracic Aortic Aneurysms leading to acute aortic Dissections (TAAD). The genetic causes of BAV remain largely unknown due to the substantial genetic and clinical heterogeneity of complications related to BAV. We determined that rare Copy Number Variants (CNVs) are significantly enriched in BAV patients who experienced early onset clinical complications. The overall goal of my research is to identify causal genetic variants that are responsible for both the BAV and its complications, and to establish the clinical phenotypes that are associated with each new gene.
The specific aims of my proposal are: 1) to characterize a cohort of BAV patients with severe and early onset complications, 2) to identify rare CNVs that are associated with severe BAV-related complications and 3) to identify rare exome sequence variants in patients with severe phenotypes or distinctive clinical features who have available parents or affected relatives. Our discoveries could provide new insights into the etiology of BAV disease and may also be useful for risk stratification or clinical decision-making about surveillance and elective interventions for BAV patients.
Bicuspid Aortic Valve (BAV) is the most common congenital heart defect. BAV affects 1% of the adult population, but is responsible up to 50% of aortic valve replacements and 10% of fatal acute aortic dissections. The goal of the proposed research is to reduce the morbidity and mortality related to BAV by identifying individuals who are genetically predisposed to early onset complications and may benefit from intensified screening, medical therapies or prophylactic surgical interventions.
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| Alhafez, Bader Aldeen; Truong, Van Thi Thanh; Ocazionez, Daniel et al. (2018) Aortic arch tortuosity, a novel biomarker for thoracic aortic disease, is increased in adults with bicuspid aortic valve. Int J Cardiol : |
