title: Improved detection of germline mutations in the von Hippel-Lindau disease tumor suppressor gene.
abstract: von Hippel-Lindau disease (VHL) is an inherited neoplastic disorder characterized by the development of tumors in the eyes, brain, spinal cord, inner ear, adrenal gland, pancreas, kidney, and epididymis. The VHL tumor suppressor gene was identified in 1993. Initial studies reported the detection of germline mutations in the VHL gene in 39-75% of VHL families. We used tests that detect different types of mutations to improve the frequency of detection of germline mutations in VHL families. The methods included quantitative Southern blotting to detect deletions of the entire VHL gene, Southern blotting to detect gene rearrangements, fluorescence in situ hybridization (FISH) to confirm deletions, and complete sequencing of the gene. Here we report that we have detected germline mutations in the VHL gene in 100% (93/93) of VHL families tested. In addition, we describe 13 novel intragenic VHL germline mutations. With the methodology described in this article, it is now possible to identify germline mutations in virtually all families with VHL.
authors.affiliation: Genetic Diagnostic Laboratory, University of Pennsylvania, Philadelphia, USA.
authors.forename: C
authors.initials: C
authors.lastname: Stolle
authors.forename: G
authors.initials: G
authors.lastname: Glenn
authors.forename: B
authors.initials: B
authors.lastname: Zbar
authors.forename: J S
authors.initials: JS
authors.lastname: Humphrey
authors.forename: P
authors.initials: P
authors.lastname: Choyke
authors.forename: M
authors.initials: M
authors.lastname: Walther
authors.forename: S
authors.initials: S
authors.lastname: Pack
authors.forename: K
authors.initials: K
authors.lastname: Hurley
authors.forename: C
authors.initials: C
authors.lastname: Andrey
authors.forename: R
authors.initials: R
authors.lastname: Klausner
authors.forename: W M
authors.initials: WM
authors.lastname: Linehan
mesh_terms: D015139:Blotting, Southern / Q000379:methods; D004252:DNA Mutational Analysis / Q000379:methods; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008025:Ligases; D011506:Proteins / Q000235:genetics*; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000235:genetics*
chemical_list: D011506:Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human