title: Sequence variations in the von Hippel-Lindau tumor suppressor gene in patients with intracranial aneurysms.
abstract: BACKGROUND
  The rupture of intracranial aneurysms leads to subarachnoid hemorrhage, which is often associated with poor outcome. Preventive treatment of unruptured intracranial aneurysms is possible and recommended. However, the lack of candidate genes precludes identifying patients at risk by genetic analyses. We observed intracranial aneurysms in 2 patients with von Hippel-Lindau (VHL) disease and the known disease-causing mutation c.292T > C (p.Tyr98His) in the VHL tumor suppressor gene. This study investigates whether the VHL gene is a possible candidate gene for aneurysm formation.
  
  
  METHODS
  Patients with intracranial aneurysms admitted to our department between 2006 and 2009 were enrolled. The peripheral leukocyte DNA of 200 patients was investigated for sequence variations in the VHL gene using denaturing high performance liquid chromatography. Peripheral leukocyte DNA of 100 randomly sampled probands was investigated as a control group. The allelic frequencies of sequence variations between both groups were compared using the Fisher exact test.
  
  
  RESULTS
  Fourteen of 200 patients with intracranial aneurysms had sequence variations at 6 different loci in the VHL gene. In contrast, no sequence variations were identified in 100 probands in the control group (P = 0.0062). However, none of the single-sequence variations had a statistically significant difference in the allelic frequencies compared to the control group.
  
  
  CONCLUSIONS
  There is accumulating evidence for a genetic basis of aneurysm development. Our investigations lead to the conclusion that the VHL gene is potentially involved in the formation of intracranial aneurysms in a subset of patients. Additional candidate genes need to be identified in order to develop sensitive genetic screening for at-risk patients.
authors: Department of Neurosurgery, Freiburg University Medical Center, Freiburg, Germany.
authors: Jan-Helge
authors: JH
authors: Klingler
authors: Marie T
authors: MT
authors: Krüger
authors: Johannes R
authors: JR
authors: Lemke
authors: Cordula
authors: C
authors: Jilg
authors: Vera
authors: V
authors: Van Velthoven
authors: Josef
authors: J
authors: Zentner
authors: Hartmut P H
authors: HP
authors: Neumann
authors: Sven
authors: S
authors: Gläsker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D002532:Intracranial Aneurysm / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D055815:Young Adult
chemical_list: D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human