title: Von Hippel-Lindau disease: a genetic study.
abstract: Genetic aspects of von Hippel-Lindau (VHL) disease were studied in familial and isolated cases. Complex segregation analysis with pointers was performed in 38 kindreds with two or more affected members. Dominant inheritance with almost complete penetrance in the highest age classes (0.96 at 51 to 60 and 0.99 at 61 to 70 years) was confirmed and there was no evidence of heterogeneity between families ascertained through complete and incomplete selection. The point prevalence of heterozygotes in East Anglia was 1.89/100,000 (1/53,000) persons with an estimated birth incidence of 2.73/100,000 (1/36,000) live births. Reproductive fitness was 0.83. Direct and indirect estimates of the mutation rate were 4.4 (95% CI 0.9 to 7.9) x 10(-6)/gene/generation and 2.32 x 10(-6)/gene/generation respectively. There was no significant association between parental age or birth order and new mutations for VHL disease.
authors.affiliation: Cambridge University, Department of Pathology.
authors.forename: E R
authors.initials: ER
authors.lastname: Maher
authors.forename: L
authors.initials: L
authors.lastname: Iselius
authors.forename: J R
authors.initials: JR
authors.lastname: Yates
authors.forename: M
authors.initials: M
authors.lastname: Littler
authors.forename: C
authors.initials: C
authors.lastname: Benjamin
authors.forename: R
authors.initials: R
authors.lastname: Harris
authors.forename: J
authors.initials: J
authors.lastname: Sampson
authors.forename: A
authors.initials: A
authors.lastname: Williams
authors.forename: M A
authors.initials: MA
authors.lastname: Ferguson-Smith
authors.forename: N
authors.initials: N
authors.lastname: Morton
mesh_terms: D000328:Adult; D001722:Birth Order; D004739:England / Q000453:epidemiology; D005298:Fertility; D005799:Genes, Dominant; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009154:Mutation; D010290:Parents; D015995:Prevalence; D012306:Risk; D006623:von Hippel-Lindau Disease / Q000235:genetics*