title: DNA-based presymptomatic diagnosis for the von Hippel-Lindau disease by linkage analysis.
abstract: Von Hippel-Lindau (VHL) disease is an autosomal dominantly inherited condition characterized by a predisposition to the development of haemangioblastoma, renal cell carcinoma and phaeochromocytoma. The gene which, when altered, causes the disease was cloned in 1993, and maps within a series of known polymorphic loci in the 3p25-p26 region. To optimize a DNA-based presymptomatic diagnosis, we have selected six highly informative microsatellite loci, closely linked to the VHL gene. Genotyping using a multiplex-PCR approach was performed in 26 affected families including 99 asymptomatic relatives born from an affected parent. Ninety-six subjects were informative with one or more markers, 76 being informative with markers on both sides of the gene. Combination of age-related and DNA-based risk information improved the accuracy of risk assessment for 90 at-risk patients (91%) and allowed attribution of risk with a confidence limit higher than 0.98 in 79 cases (88%).
authors.affiliation: Laboratoire de Génétique des Tumeurs, INSERM U434, Institut Curie, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Olschwang
authors.forename: C
authors.initials: C
authors.lastname: Boisson
authors.forename: S
authors.initials: S
authors.lastname: Richard
authors.forename: F
authors.initials: F
authors.lastname: Resche
authors.forename: G
authors.initials: G
authors.lastname: Thomas
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D004276:DNA, Satellite / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor; D008040:Genetic Linkage; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008025:Ligases; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D004276:DNA, Satellite; D005819:Genetic Markers; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human