title: Genotype-phenotype correlations in families with deletions in the von Hippel-Lindau (VHL) gene.
abstract: Von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome characterized by predisposition for bilateral and multi-centric hemangioblastoma in the retina and central nervous system, pheochromocytoma, renal cell carcinoma, and cysts in the kidney, pancreas, and epididymis. We describe five families for which direct sequencing of the coding region of the VHL gene had failed to identify the family-specific mutation. Further molecular analysis revealed deletions involving the VHL gene in each of these families. In four families, partial deletions of one or more exons were detected by Southern blot analysis. In the fifth family, FISH analysis demonstrated the deletion of the entire VHL gene. Our results show that (quantitative) Southern blot analysis is a sensitive method for detecting germline deletions of the VHL gene and should be implemented in routine DNA diagnosis for VHL disease. Our data support the previously established observation that families with a germline deletion have a low risk for pheochromocytoma. Further unraveling of genotype-phenotype correlations in VHL disease has revealed that families with a full or partial deletion of the VHL gene exhibit a phenotype with a preponderance of central nervous system hemangioblastoma.
authors.affiliation: Department of Medical Genetics, University Medical Center, Utrecht, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Hes
authors.forename: R
authors.initials: R
authors.lastname: Zewald
authors.forename: T
authors.initials: T
authors.lastname: Peeters
authors.forename: R
authors.initials: R
authors.lastname: Sijmons
authors.forename: T
authors.initials: T
authors.lastname: Links
authors.forename: J
authors.initials: J
authors.lastname: Verheij
authors.forename: G
authors.initials: G
authors.lastname: Matthijs
authors.forename: E
authors.initials: E
authors.lastname: Leguis
authors.forename: G
authors.initials: G
authors.lastname: Mortier
authors.forename: K
authors.initials: K
authors.lastname: van der Torren
authors.forename: M
authors.initials: M
authors.lastname: Rosman
authors.forename: C
authors.initials: C
authors.lastname: Lips
authors.forename: P
authors.initials: P
authors.lastname: Pearson
authors.forename: R
authors.initials: R
authors.lastname: van der Luijt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001530:Belgium; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000473:pathology; D005260:Female; D016147:Genes, Tumor Suppressor; D005838:Genotype; D018095:Germ-Line Mutation; D018325:Hemangioblastoma / Q000235:genetics / Q000473:pathology; D006801:Humans; D008025:Ligases; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010641:Phenotype; D010673:Pheochromocytoma / Q000235:genetics / Q000473:pathology; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins; D014421:Turkey / Q000208:ethnology; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000235:genetics* / Q000473:pathology
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