SMAD4 and hereditary hemorrhagic telangiectasia: HHT is an autosomal dominant vascular disorder caused by the loss-of-expression or loss-of-function mutations in the mediators of the BMP signaling pathway, such as Acvrl1, Endoglin, and Smad4. 41Nonsynonymous mutations in the Drosha-NTR, such as P32L, P100L, K226E, and R279L, have been identified in individuals with HHT without other mutations associated with HHT.16