SMAD4 and hereditary hemorrhagic telangiectasia: In addition, mutations in SMAD4 (encoding the transcription factor Smad4) have been described in a subset of HHT patients which present a juvenile polyposis/HHT overlap syndrome (JP-HHT, OMIM #175050) but the frequency of these mutations does not exceed 2% of the HHT patient population [14–16].