Background: : Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease mainly causedby mutations of the adenomatous polyposis coli (APC) gene with almost complete penetrance. These colorectalpolyps are precancerous lesions that will inevitable develop into colorectal cancer at the median age of 40-yearold if total proctocolectomy is not performed. So identification of APC germline mutations has great implicationsfor genetic counseling and management of FAP patients. In this study, we screened APC germline mutationsin Chinese FAP patients, in order to find novel mutations and the APC gene germline mutation characteristicsof Chinese FAP patients. Materials and
Methods: The FAP patients were diagnosed by clinical manifestations,family histories, endoscope and biopsy. Then patients peripheral blood samples were collected, afterwards,genomic DNA was extracted. The mutation analysis of the APC gene was conducted by direct polymerasechain reaction (PCR) sequencing for micromutations and multiplex ligation-dependent probe amplification(MLPA) for large duplications and/or deletions.
Results: We found 6 micromutations out of 14 FAP pedigrees,while there were no large duplications and/or deletions found. These germline mutations are c.5432C>T(p.Ser1811Leu), two c.3926_3930delAAAAG (p.Glu1309AspfsX4), c.3921_3924delAAAA (p.Ile1307MetfsX13),c3184_3187delCAAA(p.Gln1061AspfsX59) and c4127_4126delAT (p.Tyr1376LysfsX9), respectively, and alldeletion mutations resulted in a premature stop codon. At the same time, we found c.3921_3924delAAAA andtwo c.3926_3930delAAAAG are located in AAAAG short tandem repeats, c3184_3187delCAAA is located in theCAAA interrupted direct repeats, and c4127_4128 del AT is located in the 5’-CCTGAACA-3’ ,3’-ACAAGTCC-5palindromes (inverted repeats) of the APC gene. Furthermore, deletion mutations are mostly located at condon1309.
Conclusions: Though there were no novel mutations found as the pathogenic gene of FAP in this study,we found nucleotide sequence containing short tandem repeats and palindromes (inverted repeats), especiallythe 5 bp base deletion at codon 1309, are mutations in high incidence area in APC gene.