Background: Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder caused by germline mutations in the APC gene. FAP is characterised by a variable, but normally large number of colorectal adenomas and variations in extracolonic manifestations. These variations are associated with specific mutations of the APC gene.
Material and methods: Representatives from 70 Norwegian families are under molecular investigation. Analyses have so far been concentrated on the part of the APC gene associated with classic FAP.
Results: Germline mutations causing FAP have been identified in 36 of the 70 families examined. All mutations identified are confined to the first half of the gene and correlate to classic FAP.
Interpretation: Because of the mutation heterogeneity in FAP, the size of the APC gene and variations in phenotype, it is a laborious task to identify the causative mutations. Better approaches to the analysis of the whole APC have now been established and will result in a higher degree of mutation detection independent of phenotype. Family history and phenotype-genotype correlations are still important guidelines for efficient molecular genetic analysis of the APC gene. Genetic surveillance, personal and socio-economic benefits from presymptomatic and predictive testing of members of FAP families are discussed.