Pedigree analysis and study of germline mutations in the APC gene in a kindred with familial adenoma-tous polyposis

Abstract

Objective To explore the significance of pedigree analysis and gene screening for the atrisk membership of a kindred with familial adenomatous polyposis (FAP) , and to report the results of germline mutations in the APC gene that predispose the disease susceptibility in the kindred with FAP from Yunnan Province. Methods Using a patient with FAP as index patient, the pedigree and all lineal and collateral relatives were interviewed, and then pedigree was protracted. Genomic DNA was extracted from the peripheral blood leukocytes of individuals from the family and the APC gene was screened for germline mutations by using PCR and DNA direct sequencing. Results Among the nine individuals subjected to genetic analysis of the APC gene from the family, mutation was detected in eight, which is the C to A transversion resulting in a stop codon at codon 1196(TCA >TAA,c.3587C >A) within exon 15. Family membersⅡ2、Ⅱ3、Ⅱ4、Ⅲ2、Ⅲ3 were found positive for multiple polyps using colonoscopy.Ⅲ4 was a gene mutation carrier but does not have any polyps. Conclusion Patient with FAP can be diagnosed early by genetic counseling and thus gene screening for the at-risk relatives in FAP family. It is very helpful in particular for the APC gene mutation carriers and pre-symptomatic. Preventive treatment can be done to reduce the rate of malignant transformation and mortality of FAP. In this study, genomic mutation (p. S1196X) of the APC was confirmed to be pathogenic, which was similar to the previous reports in other areas. Key words: Familial adenomatous polyposis; Adenomatous polyposis coli gene; Family survey; Germline mutation