GENOTYPE-PHENOTYPE CORRELATION BETWEEN POSITION OF CONSTITUTIONAL APCGENE 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 in herited predispostion to colorectal cancer. The most common extracolon ic manifestation is congenital hypertrophy of the retinal pigment epit helium (CHRPE), expressed in up to 90% of FAP kindreds. Chain-terminat ing APC mutations were characterised in 26 unrelated FAP patients. Res ults show that CHRPE expression is determined by the length of truncat ed protein product. CHRPE is therefore the first extracolonic manifest ation of FAP to be shown to be un der the control of the APC mutation site and should facilitate the detection of constitutional APC mutatio ns in FAP kindreds.