title: Analysis of genetic and phenotypic heterogeneity in juvenile polyposis.
abstract: BACKGROUND
  Juvenile polyposis syndrome (JPS) is characterised by gastrointestinal (GI) hamartomatous polyposis and an increased risk of GI malignancy. Juvenile polyps also occur in the Cowden (CS), Bannayan-Ruvalcaba-Riley (BRRS) and Gorlin (GS) syndromes. Diagnosing JPS can be problematic because it relies on exclusion of CS, BRRS, and GS. Germline mutations in the PTCH, PTEN and DPC4 (SMAD4) genes can cause GS, CS/BRRS, and JPS, respectively.
  
  
  OBJECTIVE
  To examine the contribution of mutations in PTCH, PTEN, and DPC4 (SMAD4) to JPS.
  
  
  METHODS
  Forty seven individuals from 15 families and nine apparently sporadic cases with JPS were screened for germline mutations in DPC4, PTEN, and PTCH.
  
  
  RESULTS
  No patient had a mutation in PTEN or PTCH. Five different germline mutations were detected in DPC4; three of these were deletions, one a single base substitution creating a stop codon, and one a missense change. None of these patients had distinguishing clinical features.
  
  
  CONCLUSIONS
  Mutations in PTEN and PTCH are unlikely to cause juvenile polyposis in the absence of clinical features indicative of CS, BRRS, or GS. A proportion of JPS patients harbour DPC4 mutations (21% in this study) but there remains uncharacterized genetic heterogeneity in JPS.
authors.affiliation: Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, UK.
authors.forename: K
authors.initials: K
authors.lastname: Woodford-Richens
authors.forename: S
authors.initials: S
authors.lastname: Bevan
authors.forename: M
authors.initials: M
authors.lastname: Churchman
authors.forename: B
authors.initials: B
authors.lastname: Dowling
authors.forename: D
authors.initials: D
authors.lastname: Jones
authors.forename: C G
authors.initials: CG
authors.lastname: Norbury
authors.forename: S V
authors.initials: SV
authors.lastname: Hodgson
authors.forename: D
authors.initials: D
authors.lastname: Desai
authors.forename: K
authors.initials: K
authors.lastname: Neale
authors.forename: R K
authors.initials: RK
authors.lastname: Phillips
authors.forename: J
authors.initials: J
authors.lastname: Young
authors.forename: B
authors.initials: B
authors.lastname: Leggett
authors.forename: M
authors.initials: M
authors.lastname: Dunlop
authors.forename: P
authors.initials: P
authors.lastname: Rozen
authors.forename: C
authors.initials: C
authors.lastname: Eng
authors.forename: D
authors.initials: D
authors.lastname: Markie
authors.forename: M A
authors.initials: MA
authors.lastname: Rodriguez-Bigas
authors.forename: E
authors.initials: E
authors.lastname: Sheridan
authors.forename: T
authors.initials: T
authors.lastname: Iwama
authors.forename: D
authors.initials: D
authors.lastname: Eccles
authors.forename: G T
authors.initials: GT
authors.lastname: Smith
authors.forename: J C
authors.initials: JC
authors.lastname: Kim
authors.forename: K M
authors.initials: KM
authors.lastname: Kim
authors.forename: J R
authors.initials: JR
authors.lastname: Sampson
authors.forename: G
authors.initials: G
authors.lastname: Evans
authors.forename: S
authors.initials: S
authors.lastname: Tejpar
authors.forename: W F
authors.initials: WF
authors.lastname: Bodmer
authors.forename: I P
authors.initials: IP
authors.lastname: Tomlinson
authors.forename: R S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000175:diagnosis / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D018388:Codon, Terminator / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D017353:Gene Deletion; D018740:Genetic Heterogeneity; D005820:Genetic Testing; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D051059:PTEN Phosphohydrolase; D010641:Phenotype; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D025521:Tumor Suppressor Proteins
chemical_list: D018388:Codon, Terminator; D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human