Transforming Growth factor β 2 Mutations and Familial Thoracic Aortic Aneurysms

Abstract

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. 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 …