FBN1 and Marfan syndrome: First, the existence of increased circulating TGF-β1 activity and concentration in other connective tissue disorders such as heterotopic ossification, characterized by ectopic bone formation in extraskeletal tissues and Marfan syndrome, caused by mutations in fibrillin-1, an ECM protein (Matt et al., 2009; Franken et al., 2013; Wang et al., 2018).