title: Broad phenotypic spectrum in familial adenomatous polyposis; from early onset and severe phenotypes to late onset of attenuated polyposis with the first manifestation at age 72.
abstract: BACKGROUND
  Familial adenomatous polyposis (FAP) is typically characterized by multiple colonic polyps and frequent extracolonic features. Whereas the number of colonic polyps has been linked to the APC gene mutation, possible genotype-phenotype correlations largely remain to be defined for the extracolonic manifestations.
  
  
  METHODS
  Full genomic sequencing combined with multiplex ligation-dependent probe amplification was used to identify APC gene mutations, which were correlated to the clinical presentations.
  
  
  RESULTS
  10 novel APC gene mutations were identified in 11 families. A broad spectrum of extracolonic manifestations was identified in most of these individuals. Two sisters with an insertion in codon 528 (c.1582_1583insGC) both showed severe phenotypes with classical polyposis, upper gastrointestinal polyps and thyroid cancer. A woman with a 3'APC mutation (c.5030_5031insAA) developed colon cancer at age 72 as the first manifestation of attenuated FAP.
  
  
  CONCLUSIONS
  With an increasing number of FAP families diagnosed, a broad and variable tumor spectrum and a high frequency of extracolonic manifestations are gradually recognized. We report novel APC mutations and present two FAP cases that suggest familial aggregation of thyroid cancer and demonstrate the need to consider attenuated FAP also among elderly patients with colon cancer.
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Lund University, Sweden. mef.nilbert@med.lu.se
authors.forename: Mef
authors.initials: M
authors.lastname: Nilbert
authors.forename: Ulf
authors.initials: U
authors.lastname: Kristoffersson
authors.forename: Mats
authors.initials: M
authors.lastname: Ericsson
authors.forename: Oskar
authors.initials: O
authors.lastname: Johannsson
authors.forename: Eva
authors.initials: E
authors.lastname: Rambech
authors.forename: Peter
authors.initials: P
authors.lastname: Mangell
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000453:epidemiology / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D005091:Exons; D005260:Female; D017491:Genes, APC; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D055815:Young Adult