Causative gene mutations (for example, NOTCH1, SMAD6) are known for ≤1% of nonsyndromic BAV cases with and without AscAA<sup>5-8</sup>, impeding mechanistic insight and development of therapeutic strategies.
Deregulation of Notch1 pathway and circulating endothelial progenitor cell (EPC) number in patients with bicuspid aortic valve with and without ascending aorta aneurysm.
These findings are the first to our knowledge to demonstrate an SHF lineage-specific role for Notch1 in AscAA and suggest that genes linked to the development of BAV may also contribute to the associated aortopathy.
Corroborating previous studies, analysis of the single sporadic patient with calcified aortic valve in the presence of ascending aortic aneurysm revealed a novel heterozygous missense mutation in NOTCH1 resulting in a nonsynonymous amino acid substitution (p.T1090S, c.C3269G) of an evolutionarily conserved residue.