Germline mutation at codon 1309 of the adenomatous polyposis coli gene and exteracolonic manifestations in familial adenomatous polyposis

Background: Familial adenomatous polyposis (FAP) is the most common components polyposis syndromes. It incidence is for less than 1 percent of colorectal cancer cases. FAP is characterized by germline mutations in the adenomatous polyposis coli (APC) gene. Generally, there are hundreds to thousands of adenomatous polyps in colon and rectum of patients. The aim of the current study was to evaluate the germline mutation at codon 1309 of the APC gene and its association with extracolonic manifestations in Iranian patients with FAP. Methods: This Cross-sectional study was conducted at the Gastroenterology and Liver Diseases Research Center, Taleghani Hospital, Tehran, Iran from July 2012 to February 2015. In this study, thirty-three patient with FAP was examined. Demographic and clinical data were gathered from patients. In addition, peripheral blood samples were collected to study the most common mutations of the APC gene and bidirectional sequencing was carried out after genomic DNA extraction by salting out method. Primers were designed by GeneRunner version 5.0.4 (http://www.generunner.com). The samples were run on an applied biosystems 3130XL genetic analyzer. The results were analyzed by SPSS software, version 23 (IBM, Armonk, NY, USA). Results: After analyzing the mutation cluster region (MCR), we have identified five germline mutations with 5bp deletion at codon 1309 of the APC gene (c.3927_3931delAAAGA), that it is equivalent to 15.2% (5.33). This mutation has been known as a small deletion, that it is a variant of frameshift mutation. Mutation at codon 1309 has significant association with clinical and pathological features including the number of polyps (P=0.001), duodenum demonstration (P=0.008), fundic gland polyp (P=0.002) and congenital hypertrophy of the retinal pigment epithelium (P=0.021). Conclusion: The analysis of the findings has shown that mutation in Codon 1309 of adenomatous polyposis coli gene may be associated with severe polyposis and extracolonic manifestations. In conclusion, there may be a correlation between a specific germline mutation and the extracolonic manifestations