APC mutation and phenotypic spectrum of Singapore familial adenomatous polyposis patients

Familial adenomatous polyposis (FAP) is a familial form of colon cancer cau sed by mutation of the adenomatous polyposis coli (APC) gene. Although the APC gene has been extensively studied in the Caucasian population, it has n ot been previously described in the Chinese population. In the present stud y, we investigated APC mutation and phenotypic spectrum in the Singapore FA P families who are predominantly Chinese. The protein truncation test (PTT) was used to screen the entire APC gene for germline mutations in 28 unrela ted families. Fifteen different mutations were identified in 22families, Ei ght mutations were 1-11 basepair deletions or insertions; three involved de letions of whole exons and four were nonsense mutations. Nine of the mutati ons, including two complex rearrangements, are novel. Eight families includ ing three de novo cases have the same (AAAGA) deletion at codon 1309, indic ating that like the Western families, codon 1309 is also the mutation 'hot spot' for Singapore FAP families. In contrast, we did not find any mutation in codon 1061, the second hot spot for the Western population. Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is consistently assoc iated with the prescribed domain (codons 463 to 1387) and is the only pheno type with no intra-family variation. Other than CHRPE, differences in the t ype and frequency of extracolonic manifestations within the FAP families su ggest the influence of modifying genes and environmental factors.