Analysis Of The Mutations Of APC Gene In A Family With Familial Adenomatous Polyposis

Colorectal carcinoma is one of the common malignant tumor in the digestive system,which could be roughly divided into sporadic and familial two types. The incidengce of Familial Adenomatous Polyposis(FAP) is 1%. Classical Familial Adenomatous Polypsis(CFAP) is an autosomal dominant genetic disease, which is characterized by the numerous adenomatous polyps and microadenoma in the colon and rectum.The polyps will increase with age, and the polyps will 100% develop to colorectal cancer if early detection or surgical treatment not be done. Studies have shown that adenomatous polyposis coli gene mutation is responsible for the incidence of FAP. In addition, some APC mutation-negative FAP patients carry a MYUTH gene or AXIN2 gene mutation as well. Therefore, DNA mutation test is a scientific and effective diagnostic method for the FAP patients and their families.Objective:The aim of the study was to screen the causative adenomatous polyposis coli(APC) gene defects associated with a clinical collected pedigree of familial adenomatous polyposis(FAP).Compare the result with reports from domestic and overseas to identify the mocular etiology of this pedigree. Offer a future help for the diagnosis and prognosis of FAP, at the same time, provide a FAP molecular diagnosis data for the future.Materials and methods :FAP patients was diagnosis by clinical manifestations,family histories, endoscopic and pathologic examinations. After receiving a written consent from the FAP patient and her family members, collect the common information,proceed clinical evaluation and complete relative inspections. Draw a family tree of this pedigree and collect blood samples of the FAP pedigree members, Cokic Polyp patientsand normal person,respectively?Then extract the genomic DNA of them and PCR the 15 exons of the APC gene.The mutation analysis of the adenomatous polyposis coli(APC)was conducted by directpolymerase chain reaction(PCR) sequenceing.Results:we found 3 synonymous mutations and a missense mutation: c. 5034 G >A(p. Gly 1678 Gly),c.5274 T > G(p. Ser 1758 Ser),c. 5465 T > A(p. Val 1822 Asp),c. 5880 G > A(p. Pro 1960 Pro),while Cokic Polyp patients and normal person don't exist these mutations. In addition, there are 2 different mutation forms exist is this pedigree: homozygous mutation and heterozygous mutation.Conclusion:The mutation on APC gene c. 5465 T > A(p. Val 1822 Asp) may be the causative gene defects of this FAP pedigree. This mutation has two forms exist in the pedigree. Comparing with the reports from domestic and overseas, the two different forms may have different influence to FAP patients.