The possible involvement of mutations in the VHL gene in aneurysm formation was supported by the fact that deregulations of various proteins and mediators occur in VHL disease that are involved in maintaining the structure of the arterial wall,18, 19, 20 including vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), collagen type III, fibronectin, elastase, laminin, alpha-1 antitrypsin, fibroblast growth factor, transforming growth factor (TGF), platelet-derived growth factor (PDGF), polycystin, fibrillin,18 and hypoxia-inducible factor (HIF).19, 20 Figure 2 reviews the effects that potentially facilitate aneurysm formation. Therefore, we investigated 200 patients with intracranial aneurysms and 100 probands of a random sample of the normal population for sequence variations in the VHL tumor suppressor gene using DHPLC.