Clinical and Genetic Characterization of Familial Adenomatous Polyposis: An Iranian Population Study

Familial adenomatous polyposis (FAP) is an inherited autosomal dominant disorder, which can develop into cancer in early adulthood (100%) and is a result of germline mutations in the adenomatous polyposis coli (APC) genes.
Identify APC germline mutations and assessed relationships between genotypes and phenotypes.
In a census-based cross-sectional study, FAP patients were selected from the referral medical centers of East Azarbaijan province between 2013 and 2016. Written informed consent was obtained from all patients for blood sampling and genetic testing. Patients undergo genetic counseling, and the pedigree was drawn. After peripheral blood sampling and DNA extraction, the potential mutation of the APC gene was detected by polymerase chain reaction (PCR), and DNA sequencing. Statistical tests were carried out using SPSS version 16.0. Categorical data between two groups were compared using chi-square test. Independent sample t- test was used for comparison of continuous variables between two groups. The P-value We identified APC gene mutations in 18 of the 30 unrelated patients with FAP (60%), including one novel frame shiftmutation, three nonsense mutations, and 14 novel missense mutations (78%). The most frequent mutations were in codon 1308 and 1350. Meanwhile, we found a novel polymorphism.
Our study results indicated that the APC gene has a high mutation detection rate (60%) between codons 999 and 1410, and codons 1308, and 1350 are two mutation hotspot regions.