Correlation between the location of germ-line mutations in the APC gene and the number of colorectal polyps in familial adenomatous polyposis patients.

TLDR

The APC gene, responsible for familial adenomatous polyposis, has been isolated and its germ‑line mutations identified in many patients. The study aimed to compare the positions of APC germ‑line mutations with the number of colorectal polyps in 22 unrelated FAP patients. Researchers examined mutation locations in 22 patients (12 previously reported) and counted polyps, distinguishing 17 sparse and 5 profuse cases. Most mutations were truncating, and those between codons 1250 and 1464 correlated with profuse polyps, implying that polyp burden may reflect differences in the stability or function of the truncated APC protein.

Abstract

Recently we have isolated the adenomatous polyposis coli (APC) gene which causes familial adenomatous polyposis (FAP), and its germ-line mutations in a substantial number of FAP patients have been identified. On the basis of this information, we compared the location of germ-line mutations in the APC gene in 22 unrelated patients (12 of whom have been reported previously) with the number of colorectal polyps developed in FAP patients; 17 were sparse types and five were profuse types. All but one of the mutations were considered to cause truncation of the gene product by frame-shift due to deletion (14 cases) or nonsense mutation (seven cases). The location of the germ-line mutations seems to correlate with the two clinical types; germ-line mutations in five FAP patients with profuse polyps were observed between codon 1250 and codon 1464, whereas mutations in 17 FAP patients with fewer polyps were observed in the other regions of the APC gene. The result suggests that the number of colorectal polyps in FAP patients may be associated with a difference in the stability or biological function of the truncated APC protein.