title: VHL P25L is not a pathogenic von Hippel-Lindau mutation: a family study.
abstract: BACKGROUND
  von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome in which affected individuals may develop CNS and retinal hemangioblastomas, pheochromocytomas, renal cell carcinoma, and cysts of various organs. The VHL gene has been localized to chromosome 3p25-26 and >500 germline mutations have been identified. A rare variant of the VHL gene results in the substitution of lysine for proline at position 25 (P25L) in the larger of the two VHL proteins. This VHL variant has previously been described in a limited number of cases and has been strongly suggested to be non-pathogenic, but this has not been proven.
  
  
  METHODS
  A family with a medical history suggestive of VHL disease was investigated using DNA sequence analysis to determine the presence of the P25L variant of the VHL protein.
  
  
  RESULTS
  Sequence analysis identified the VHL P25L variant in 7 of 14 family members, one of whom had a single retinal hemangioma, which is in itself insufficient to diagnose VHL disease. The variant was not identified in a family member with clear cell renal carcinoma, which is a hallmark feature of VHL disease.
  
  
  CONCLUSIONS
  On the basis of these results, it is concluded that P25L is a benign variant of the VHL protein and individuals carrying this variant should not be required to undergo screening for VHL manifestations.
authors.affiliation: Maritime Medical Genetics Service, IWK Health Centre, Halifax, Nova Scotia, Canada.
authors.forename: Rachel K
authors.initials: RK
authors.lastname: Pettman
authors.forename: Amy
authors.initials: A
authors.lastname: Crowley
authors.forename: Christie
authors.initials: C
authors.lastname: Riddell
authors.forename: Mark D
authors.initials: MD
authors.lastname: Ludman
mesh_terms: D000368:Aged; D019943:Amino Acid Substitution; D006801:Humans; D008239:Lysine / Q000737:chemistry / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011392:Proline / Q000737:chemistry / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*; D006623:von Hippel-Lindau Disease / Q000235:genetics* / Q000473:pathology
chemical_list: D011392:Proline; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human; D008239:Lysine