Characterization of two novel adenomatous polyposis coli (APC) gene mutations in patients with familial adenomatous polyposis (FAP).

Patients with Familial Adenomatous Polyposis (FAP) manifest numerous colorectal adenomas as well as benign and malignant extra-colonic lesions. Adenomatous polyposis coli (APC) gene mutations are the underlying genetic defect in FAP. We analyzed germline DNA of 81 unrelated FAP patients and evaluated correlation of APC mutation genotype and clinical phenotype. Germline APC mutations were identified in 18 FAP patients including two novel 2 bp deletions at APC codons 1067 and 1259. FAP patients were screened for hypertrophic ocular fundus lesions, desmoids and peri-ampullary adenomas. As reported previously (Olshwang et al 1993b), a positive correlation for the frequency of retinal lesions and germline APC mutation was observed among all FAP patients except one. No significant correlation was observed for APC mutation genotype and the occurrence of desmoids and peri-ampullary adenomas. Genetic factors contributing to familial segregation of these lesions need further investigation.