Endoglin Background Information
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by vascular abnormalities such as dilated vessels, hemorrhages, liver and lung congestion, and brain or heart ischemia. Mutations in two genes, Endoglin (also designated CD105) and ALK-1 (Activin receptor-like kinase 1, also designated TGF∫ superfamily RI), are responsible for HHT. Endoglin is mutated in HHT1, and ALK-1 is mutated in HHT2, both of which are thought to be caused by haploinsufficiency. Endoglin and ALK-1 are type III and type I members of the TGF∫ receptor superfamily, respectively, that are expressed on vascular endothelial cells. Endoglin can only bind ligands of the TGF∫ superfamily via association with the respective ligand binding receptors for TGF∫1, TGF∫3, Activin-A, BMP-2 and BMP-7. The human ALK-1 gene encodes two protein species which exist as a result of either glycosylation or alternative splicing events. ALK-1 preferentially binds TGF∫1 and is expressed in bone marrow stromal cells, lung, brain, kidney and spleen.
