GDF2 and hereditary hemorrhagic telangiectasia: In the case of ENG, two new missense mutations within the orphan domain (S278P, F282V) were recently described as inhibiting BMP9 binding to endoglin (Mallet et al., 2014) in accordance with the previous mapping of the BMP9-binding region of endoglin to its orphan domain (Castonguay et al., 2011; Alt et al., 2012) further supporting the involvement of BMP9 in HHT pathogenesis.