Nonetheless, haploinsufficiency of other TGFβ signaling components, such as the SMAD3 effector and the TGFβ2 ligand, which also leads to pathologically increased TGFβ signaling has previously been suggested as the disease mechanism causing thoracic aortic aneurysms and various associated features [24], [33], [34]. This evidence concerns the gene SMAD3 and thoracic aortic aneurysm.