Genetic Basis of Early Onset Bicuspid Aortic Valve Disease

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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.