Genotype-phenotype correlation between position of constitutional APC gene mutation and CHRPE expression in familial adenomatous polyposis

Mutations in the adenomatous polyposis coli (APC) gene are responsible for the disease familial adenomatous polyposis (FAP), a dominantly inherited predisposition to colorectal cancer. The most common extra-colonic manifestation is congenital hypertrophy of the retinal pigment epithelium (CHRPE), expressed in up to 90% of FAP kindreds. Chain-terminating APC mutations were characterised in 26 unrelated FAP patients. Results show that CHRPE expression is determined by the length of truncated protein product. CHRPE is therefore the first extracolonic manifestation of FAP to be shown to be under the control of the APC mutation site and should facilitate the detection of constitutional APC mutations in FAP kindreds.