Screening for germ‐line mutations in familial adenomatous polyposis patients: 61 new patients and a summary of 150 unrelated patients

We report here the result of a screening for germ‐line mutations in the adenomatous polyposis coli (APC) gene in 61 new familial adenomatous polyposis (FAP) patients as well as a summary of the results of 150 patients. Examination of the entire coding region of the APC gene, based on a ribonuclease protection assay coupled with the polymerase chain reaction (PCR), disclosed mutations that were considered to cause significant defects in the APC product in 97 of 150 unrelated FAP patients. Our findings revealed the following characteristics of the germ‐line mutations of APC: (1) the great majority of the mutations were found to truncate the APC product; (2) almost all of the mutations were located within the first half of the coding region; (3) no correlation was observed between the locations of germ‐line mutations and extracolonic manifestations in FAP patients; (4) more than 80% of base substitutions in the APC gene were from cytosine to other nucleotides, nearly one‐third of which occurred at the CpG site. Our results provide information helpful to an understanding of the APC gene and will also contribute to presymptomatic diagnosis of members in FAP families. © 1992 Wiley‐Liss, Inc.