Editor—Familial adenomatous polyposis (FAP) is generally considered a typical monogenic disease caused by germline mutations within the adenomatous polyposis coli (APC) gene. Despite applying several screening techniques, however, mutational studies world wide have failed to identify a germline mutation within the APC gene in up to 50% of all FAP cases (called APC negative below).1 2 Intronic alterations, mutations within the regulatory regions causing altered APC gene expression, or large scale rearrangements of the APC gene could account for the failure to identify an APC mutation in some FAP families. Assuming no hot spots, however, such mutations are not likely to cause a high percentage of APC negative cases.

Fifty families which were referred to our department with the clinical diagnosis of FAP were tested for APC germline mutations. In 14 of them (28%), no APC mutation could be identified after screening the entire coding region of the gene (APC negative group) using the protein truncation test (PTT, the whole coding region), single strand conformation polymorphism analysis (SSCP, the affected PTT segment), and direct DNA sequencing (the affected SSCP exon).3 As these families …