Mutations in ACTA2 (Actin, alpha 2, smooth muscle, aorta;10q23.3, OMIM*102620) were identified in 7 family members with aortic aneurysms and dissection, of whom 3 had BAVs, their aortic tissue displaying increased proteoglycans accumulation, fragmentation, loss of elastic fibers, and decreased numbers of smooth muscle cells, consistent with aortic wall degeneration. Here, ACTA2 is linked to aortic aneurysm.