Background: The adenomatous polyposis coli (APC) gene at chromosome 5q21 that is responsible for familial adenomatous polyposis (FAP) was recently isolated, and germ-line mutations in a substantial number of FAP families were characterized. Based on this information, the authors attempted to develop a presymptomatic diagnosis test for members of families that carry FAP.
Methods: A rapid screening procedure using a polymerase chain reaction (PCR) method without radioisotopes, if necessary, coupled with digestion of restriction enzymes has been performed by detection of germ-line mutations that alter the size of DNA fragments or affect the recognition site of restriction enzymes in the APC locus.
Results: A rapid screening procedure to detect germ-line mutations at 12 loci that cause adenomatous polyposis was established.
Conclusions: Using these 12 systems, presymptomatic diagnoses can be made with 100% accuracy within 24 hours. The procedures will be useful for counselling of members in some FAP families, which accounted for nearly 40% of the 95 FAP kindreds that have been detected by the germ-line mutations so far.