title: APC mutation spectrum of Norwegian familial adenomatous polyposis families: high ratio of novel mutations.
abstract: BACKGROUND
  Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disease caused by mutations in the adenomatous polyposis coli (APC) gene. Massive formation of colorectal adenomas, of which some will inevitably develop into adenocarcinomas, is the hallmark of the disease. Characterization of causative APC mutations allows presymptomatic diagnosis, close follow-up and prophylactic intervention in families. To date more than 900 different germline mutations have been characterized worldwide demonstrating allelic heterogeneity.
  
  
  OBJECTIVE
  The germline mutation spectrum of APC identified in 69 apparently unrelated Norwegian FAP families are presented and discussed with reference to clinical phenotype and novel mutation rate.
  
  
  METHODS
  Different methods have been used over the years. However, all mutations were confirmed detectable by an implemented denaturing high-performance liquid chromatography screening approach. Multiplex ligation-dependent probe amplification analysis was employed for potential gross rearrangements.
  
  
  RESULTS
  Fifty-three distinctive mutations were detected, of which 22 have been detected in Norway exclusively. Except for two major deletion mutations encompassing the entire APC, all mutations resulted in premature truncation of translation caused by non-sense (31%) or change in reading frame (69%).
  
  
  CONCLUSIONS
  A high ratio of novel APC mutations continues to contribute to APC mutation heterogeneity causing FAP. This is the first comprehensive report of APC germline mutation spectrum in Norway.
authors.affiliation: Pathology Division, University Hospital of Oslo-Rikshospitalet, N0027 Oslo, Norway. per.arne.andresen@rikshospitalet.no
authors.forename: Per Arne
authors.initials: PA
authors.lastname: Andresen
authors.forename: Ketil
authors.initials: K
authors.lastname: Heimdal
authors.forename: Kristin
authors.initials: K
authors.lastname: Aaberg
authors.forename: Katrine
authors.initials: K
authors.lastname: Eklo
authors.forename: Kristin
authors.initials: K
authors.lastname: Eklo
authors.forename: Sarah
authors.initials: S
authors.lastname: Ariansen
authors.forename: Alexandra
authors.initials: A
authors.lastname: Silye
authors.forename: Olav
authors.initials: O
authors.lastname: Fausa
authors.forename: Lars
authors.initials: L
authors.lastname: Aabakken
authors.forename: Stefan
authors.initials: S
authors.lastname: Aretz
authors.forename: Tor J
authors.initials: TJ
authors.lastname: Eide
authors.forename: Tobias
authors.initials: T
authors.lastname: Gedde-Dahl
mesh_terms: D000236:Adenoma / Q000235:genetics*; D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000235:genetics*; D005190:Family; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D009664:Norway; D010641:Phenotype
chemical_list: D025601:Adenomatous Polyposis Coli Protein