title: Variable phenotype of familial adenomatous polyposis in pedigrees with 3' mutation in the APC gene.
abstract: BACKGROUND
  Germline mutation in the adenomatous polyposis coli (APC) gene on chromosome 5 causes familial adenomatous polyposis. "Attenuated" phenotype has been reported with mutation in the 5' end of the gene (5' to codon 158), but genotype-phenotype relations at the 3' end (3' to codon 1596) have not been described fully.
  
  
  OBJECTIVE
  To describe and compare colorectal and extracolonic phenotypes in a case series of families with mutation in the 3' end of the APC gene.
  
  
  METHODS
  Thirty one at risk or affected members from four families with a mutation in the APC gene located at codon 1979 or 2644 were evaluated.
  
  
  RESULTS
  Variable intrapedigree colorectal phenotype was observed: some members at older age had oligopolyposis (fewer than one hundred colorectal adenomas) whereas other members had classic polyposis at young age. Colorectal cancer was diagnosed at older mean age (50 (7) years) in the four families than in classic FAP pedigrees (39 (14) years). Extracolonic lesions characteristic of FAP occurred with 3' APC mutations, but variability in intrapedigree and interpedigree extracolonic phenotype and dissociation of severity of extracolonic manifestations from number of colorectal polyps was noted.
  
  
  CONCLUSIONS
  Families with 3' mutations of the APC gene exhibit variable intrapedigree phenotype similar to the heterogeneity noted in families with proximal 5' mutations. Genotyping of FAP and oligopolyposis pedigrees can guide appropriate surveillance of the upper and lower gastrointestinal tract in affected members.
authors.affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205-2011, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Brensinger
authors.forename: S J
authors.initials: SJ
authors.lastname: Laken
authors.forename: M C
authors.initials: MC
authors.lastname: Luce
authors.forename: S M
authors.initials: SM
authors.lastname: Powell
authors.forename: G H
authors.initials: GH
authors.lastname: Vance
authors.forename: D J
authors.initials: DJ
authors.lastname: Ahnen
authors.forename: G M
authors.initials: GM
authors.lastname: Petersen
authors.forename: S R
authors.initials: SR
authors.lastname: Hamilton
authors.forename: F M
authors.initials: FM
authors.lastname: Giardiello
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D017384:Sequence Deletion