Also, mutations in the SMAD4 gene, that encodes a transcription factor of the TGF-β-signaling pathway, are responsible for a combined syndrome of juvenile polyposis (JP) and HHT (JP-HHT; MIM600993), which occurs in less than 2% of HHT patients [13]. Here, TGFB1 is linked to hereditary hemorrhagic telangiectasia.