SMAD4 and hereditary hemorrhagic telangiectasia: Genetic screening of HHT patients has identified four mutated genetic loci, all of which are involved in the TGF-β signaling pathway, including BMP9 ligand encoding gene GDF2 (HHT5 or HHT like), type I receptor ALK1 encoding gene ACVRL1 (HHT2), co-receptor endoglin encoding gene ENG (HHT1) and intracellular mediator SMAD4 encoding gene MADH4 (JP-HHT) (McAllister et al., 1994; Johnson et al., 1996; Gallione et al., 2004; Wooderchak-Donahue et al., 2013; Figure 3).