Three Novel Mutations of APC Gene Found in A Chinese Family with Familial Adenomatous Polyposis

Abstract

Objective: To identify the causative adenomatous polyposis coli (APC) gene defects associated with a pedigree of familial adenomatous polyposis (FAP). Methods: FAP was diagnosed based on clinical manifestations, family history, as well as endoscopic and pathological examinations. The blood samples of the FAP pedigree members, colonic polyp patients, and normal individuals were collected. Genomic DNA was then extracted from those samples. APC mutation analysis was conducted via direct polymerase chain reaction (PCR) sequencing. Results: Three synonymous mutations and a missense mutation were found: c.5034G>A (p.Gly1678Gly), c.5465T>A (p.Val1822Asp), c.5880G>A (p.Pro1960Pro), and c.5274T>G (p.Ser1758Ser). Among them, the homozygous mutation on APC gene c.5034G>A has been reported, while the other three mutations have not been reported in the Chinese Han population. Individuals with c.5465T>A (p.Val1822ASP) missense mutation eventually suffer from colon cancer and have poor prognosis. We found no mutation in patients with simple intestinal polyp and in normal individuals. In addition, there were homozygous and heterozygous mutations in different patients from the same family. Conclusion: Three new mutations of APC gene were firstly reported in Han population. The missense mutation of c.5465T>A (p.Val1822Asp) may be the cause of carcinogenesis in this FAP pedigree with poor prognosis.