Ruptured intracranial aneurysm associated with von Hippel–Lindau syndrome: a molecular link?

Abstract

The VHL tumor suppressor gene may be causally related to aneurysm formation through the effects of transcription factors, growth factors, and matrix metalloproteinases. Although a single point mutation is unlikely to be responsible for the complex phenotype of intracranial aneurysm, further research on aneurysmal domes and VHL gene expression may help validate the theory that extracellular matrix destruction is the final common pathway to aneurysm formation.

Sequence Variations in the von Hippel–Lindau Tumor Suppressor Gene in Patients with Intracranial Aneurysms

“…Our observations and reports of other patients in the literature 20,44 lead to the conclusion that the VHL gene is potentially involved in the formation of intracranial aneurysms in a subset of patients. However, it is most likely not responsible for the majority of aneurysms, and additional candidate genes need to be identified in order to develop sensitive genetic screening for at-risk patients.…”

“…20,44 Gelis et al 44 reported a 26-year-old patient with a ruptured aneurysm of the middle cerebral artery and genetically proven VHL disease. Sharma and Jha 20 reported a 17-year-old girl who suffered SAH of a right posterior communicating artery aneurysm.…”

“…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.…”

“…17 In addition, the VHL gene regulates various proteins and mediators that are involved in maintaining the structure of the arterial wall. [18][19][20] The VHL gene has not been subject to genetic analyses in patients with intracranial aneurysms. Therefore, to elucidate a possible role for the VHL gene as a candidate gene for aneurysm formation, we systematically investigated a series of patients with intracranial aneurysms for sequence variations in the VHL gene and compared it to a randomly sampled control group.…”