Establishing A Genetic Diagnosis System For FAP And Analyzing Gene Mutation Detection For Three Familial Adenomatous Polyposis Syndrome Families

Background:Familial adenomatous polyposis (FAP) is a inherited syndrome of colorectal multiple denomatous polyposis predisposition because a germline mutation in the APC gene(dominantly,autosomal dominant inheritance) or MUTYH gene(autosomal recessive inheritance). FAP incidence is 1 in 8000 to 12,000 live births(prevalence is about 1 in 24,000).The coding region of APC consists of 15 exons, encoding a protein consisting of 2843 amino acids. The APC gene is a tumour suppressor gene involved in the key Wnt regulation pathway.The APC mutation detection is very important for the patients and the individuals of the family owing to carriers of a germline mutation are almost have an 100% chance of developing colorectal cancer after having multiple (typically more than 100) adenomatous polyps. Surveillance,Choice and timing of surgery is determined by the preoperative assessment of genotype, phenotype, and family aims to estimate the risk of cancer.Objective:Establishing the standardized genetic diagnosis system.Offering the the genetic diagnose and prenatal diagnosis in the Familial adenomatous polyposis families for the future surveillance and surgery treatment.Method:Making the inspection of the mutation in the mutation cluster region owing to the APC gene is so large.And screening the whole gene region consisting of 15 exons using the touchdown and gradient PCR. Main methods include polymerase chain reaction and DNA Direct sequencing,RT-PCR, microsatellite linkage analysis,etc.Result:The result of APC genetic inspection shows that two different mutations exist in the two pedigrees,and a new synonymous mutation has been detected in one pedigree;Taking a prenatal diagnosis for one FAP pedigree successfully.The mutation of c.795 ins G (p. Gly265fs X 276) in APC exon 7 was detected in pedigree 1, c.3183₃187de1(ACAAA)(p.Lys1061fs) of exon 15 was detected in pedigree 2, c.2628C>T(p. Arg876X) of exon 15 was detected in pedigree 3.Conclusion:(1 Establishing the standardized genetic diagnosis system for Familial adenomatous polyposis,providing clinical genetics counseling information and prenatal diagnosis information for the future surveillance and surgery treatment of FAP patients,and successfully making genetic diagnosis for two pedigrees and prenatal diagnosis for one pedigree.(2) Detecting a novel mutation in one pedigree.