title: Novel germline APC mutations in Swedish patients with familial adenomatous polyposis and Gardner syndrome.
abstract: BACKGROUND
  Familial adenomatous polyposis (FAP) is a familial cancer syndrome in which affected individuals develop multiple adenomatous polyps and are thereby at greatly increased risk of developing colorectal cancer. Gardner syndrome is a variant of FAP, in which the patients also develop extraintestinal tumors, in particular osteomas and desmoid tumors. An attenuated form of the disease (AFAP) is associated with fewer polyps, but still a high risk for colorectal cancer. Germline mutations in the adenomatosis polyposis coli (APC) gene cause FAP and Gardner syndrome and have recently been associated also with the development of AFAP.
  
  
  METHODS
  We have analysed the entire APC gene for germline mutations in 7 patients with FAP and in 6 patients with suspected AFAP. Mutation screening was performed by direct sequencing of exons 1-14 and using the protein truncation test for analysis of exon 15.
  
  
  RESULTS
  Novel disease-causing germline mutations, all of which resulted in truncation of the APC protein, were identified in 6 of the 7 patients with FAP or Gardner syndrome. No APC mutation was detected in any of the 6 patients with suspected AFAP.
  
  
  CONCLUSIONS
  This study reports novel FAP- and Gardner syndrome-causing mutations in the APC gene. The lack of APC mutations in patients with multiple polyps at young age indicates that other genetic defects may cause this phenotype.
authors.affiliation: Dept. of Oncology, University Hospital, Lund, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Nilbert
authors.forename: J
authors.initials: J
authors.lastname: Fernebro
authors.forename: U
authors.initials: U
authors.lastname: Kristoffersson
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D004252:DNA Mutational Analysis; D005736:Gardner Syndrome / Q000235:genetics*; D017491:Genes, APC / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D017354:Point Mutation; D013548:Sweden