title: Confirmation of FWT1 as a Wilms' tumour susceptibility gene and phenotypic characteristics of Wilms' tumour attributable to FWT1.
abstract: A susceptibility gene for Wilms' tumour (WT), designated FWT1, was previously mapped to chromosome 17q12-q21 by linkage analysis of a single family. We now confirm the existence of this gene by analysis of additional cases in the original family (3-point LOD score=5.69), and by detecting strong evidence of linkage to this region in an unrelated pedigree with seven cases of WT (3-point LOD score=2.56). Analysis of 11 smaller WT families confirms that there is genetic heterogeneity in familial WT, as three families exhibit strong evidence against linkage to FWT1. One of these was subsequently found to have a predisposing WT1 mutation. However, the other two families show evidence against both FWT1 and WT1, suggesting that at least one further familial WT gene exists. Analysis of the phenotype of 16 WT cases from the families linked to FWT1 demonstrates that they present at a significantly older age and a significantly later stage than both sporadic WT and the six cases from two families unlinked to either FWT1 or WT1. The results confirm the role of FWT1 in susceptibility to WT, provide strong evidence for genetic heterogeneity in familial WT and suggest there are phenotypic differences between familial WT due to FWT1, familial WT due to other genes and non-familial WT.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton, UK. nazneen@icr.ac.uk
authors.forename: N
authors.initials: N
authors.lastname: Rahman
authors.forename: F
authors.initials: F
authors.lastname: Abidi
authors.forename: D
authors.initials: D
authors.lastname: Ford
authors.forename: L
authors.initials: L
authors.lastname: Arbour
authors.forename: E
authors.initials: E
authors.lastname: Rapley
authors.forename: P
authors.initials: P
authors.lastname: Tonin
authors.forename: D
authors.initials: D
authors.lastname: Barton
authors.forename: G
authors.initials: G
authors.lastname: Batcup
authors.forename: J
authors.initials: J
authors.lastname: Berry
authors.forename: F
authors.initials: F
authors.lastname: Cotter
authors.forename: V
authors.initials: V
authors.lastname: Davison
authors.forename: M
authors.initials: M
authors.lastname: Gerrard
authors.forename: E
authors.initials: E
authors.lastname: Gray
authors.forename: R
authors.initials: R
authors.lastname: Grundy
authors.forename: M
authors.initials: M
authors.lastname: Hanafy
authors.forename: D
authors.initials: D
authors.lastname: King
authors.forename: I
authors.initials: I
authors.lastname: Lewis
authors.forename: A
authors.initials: A
authors.lastname: Ridolfi Luethy
authors.forename: L
authors.initials: L
authors.lastname: Madlensky
authors.forename: J
authors.initials: J
authors.lastname: Mann
authors.forename: A
authors.initials: A
authors.lastname: O'Meara
authors.forename: T
authors.initials: T
authors.lastname: Oakhill
authors.forename: M
authors.initials: M
authors.lastname: Skolnick
authors.forename: L
authors.initials: L
authors.lastname: Strong
authors.forename: M R
authors.initials: MR
authors.lastname: Stratton
mesh_terms: D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D005260:Female; D016162:Genes, Wilms Tumor / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D010641:Phenotype; D009396:Wilms Tumor / Q000235:genetics*
chemical_list: D005819:Genetic Markers