title: Hemangioblastomas of central nervous system: molecular genetic analysis and clinical management.
abstract: OBJECTIVE
  Hemangioblastomas of the central nervous system (CNS) are benign neoplasms that may occur sporadically or in association with von Hippel-Lindau (VHL) disease. The proportion of primary symptomatic hemangioblastomas associated with VHL disease is estimated to be from 10 to 40%, but it seems to be underestimated. We investigated the frequency of VHL germline mutation in patients with symptomatic CNS hemangioblastoma without evidence of VHL disease to define the role of molecular genetic analysis in the management of such patients and their relatives.
  
  
  METHODS
  We analyzed 14 patients (6 female and 8 male; mean age, 43.5 yr) with no family history and no other clinical manifestations of VHL disease who had been operated on for symptomatic CNS hemangioblastoma. Exons 1, 2, and 3 of the VHL gene and their immediately flanking sequences were amplified by use of polymerase chain reaction followed by analysis with denaturing high-performance liquid chromatography and sequencing the anomalous samples.
  
  
  RESULTS
  Germline mutations of the VHL gene were identified in 2 (14%) of 14 patients. VHL gene mutation analysis was performed in both patients' family members, which showed another affected asymptomatic subject for VHL disease. The affected subjects were recommended for VHL disease surveillance protocol.
  
  
  CONCLUSIONS
  Molecular genetic analysis is a safer and more specific instrument to confirm or exclude VHL disease in patients with CNS hemangioblastoma, a negative family history, or absence of other known manifestations of the disease. Early identification of VHL mutation gene carriers is important for reducing disease morbidity and mortality. Nonsymptomatic family members will benefit from early VHL disease diagnosis or by being excluded as at-risk subjects, reducing the psychological and economic burden of screening and surveillance protocols.
authors.affiliation: Casa Sollievo della Sofferenza Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, San Giovanni Rotondo, Italy. domenicocatapano@libero.it
authors.forename: Domenico
authors.initials: D
authors.lastname: Catapano
authors.forename: Lucia Anna
authors.initials: LA
authors.lastname: Muscarella
authors.forename: Vito
authors.initials: V
authors.lastname: Guarnieri
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Zelante
authors.forename: Vincenzo Antonio
authors.initials: VA
authors.lastname: D'Angelo
authors.forename: Leonardo
authors.initials: L
authors.lastname: D'Agruma
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000235:genetics; D016543:Central Nervous System Neoplasms / Q000175:diagnosis / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons; D005260:Female; D018325:Hemangioblastoma / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007930:Leucine / Q000235:genetics; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D008967:Molecular Biology; D020125:Mutation, Missense; D011392:Proline / Q000235:genetics; D012189:Retrospective Studies; D014364:Tryptophan / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D006623:von Hippel-Lindau Disease / Q000235:genetics
chemical_list: D014364:Tryptophan; D001120:Arginine; D011392:Proline; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human; D007930:Leucine