Transforming Growth factor β2 Mutations and Familial Thoracic Aortic Aneurysms
Previous genetic studies of patients with thoracic aortic aneurysms have identified mutations in several genes involvedin some way with transforming growth factor (TGF)-β signaling: FBN1 (encoding fibrillin-1, causing Marfan syndrome), TGFBR1 and TGFBR2 (encoding transforming growth factor-β receptors I and II, causing Loeys-Dietz syndrome), and SMAD3 (encoding Mothers against decapentaplegic homolog 3, causing aneurysms-osteoarthritis syndrome). Two groups (Boileau et al, Lindsay et al) sought to identify additional genes responsible for familial thoracic aortic aneurysms. They also sought to explain an apparent paradox: mutations in the aforementioned genes that would be predicted to result in reduced activity of the TGF-β pathwayappear to cause vasculopathy via increased TGF-β signaling.
How Was the Hypothesis Tested?
Both groups started by identifying families with autosomal dominant transmission of thoracic aortic aneurysms and in whom mutations in FBN1, TGFBR1, TGFBR2, and SMAD3 had been ruled out. Each used modern genetic techniques to identify the presumptive causal gene mutations responsible …