Familial adenomatous polyposis: more evidence for disease diversity and genetic heterogeneity

Familial adenomatous polyposis (FAP) is characterised by the presence of pr ofuse colonic carpeting of adenomas throughout the entire colon and rectum. The genetic basis of FAP has been shown to be primarily associated with ge rmline mutations in the APC gene. Notwithstanding, several reports have bee n published indicating that there is genetic heterogeneity in FAP and that the most likely explanation is the existence of another gene. In this repor t we further delineate the genotype/phenotype correlation in families that harbour germline mutations ire the APC gene and identify some previously un reported changes in the APC gene which predispose to an attenuated disease phenotype. From 53 index patients diagnosed with either FAP or attenuated F AP, 27 harboured changes in the APC gene. The remaining 26 patients were fu rther subgrouped according to their colonic phenotype. There were nine pati ents with a mixed hyperplastic/adenomatous colonic phenotype and there were 17 patients with an adenomatous colonic phenotype. Evaluation of the disea se characteristics of these patients and their families is presented which may aid in the identification of new genes associated with colonic polyposi s.