Mutations in the APC gene in Russian patients with classic form of familial adenomatous polyposis

The primary structure of the APC gene DNA was examined in 108 patients younger than 45 years old diagnosed with “familial adenomatous polyposis, classic form” using PCR, conformation-sensitive electrophoresis, and Sanger sequencing. Mutations in the APC gene were observed in 78 patients; de novo mutations were observed in 17 cases. In the majority of cases (n = 45), patients exhibited frameshift mutations, 28 patients had nonsense mutations, and other 5 patients showed splicing mutations. We also revealed recurring variants: p.Arg232X (2 cases), p.Asp849GlufsX11 (2), p.Ser1068GlyfsX57 (2), p.Arg216X (3), p.Gln1062X (5), p.Arg213X (5), and p.Glu1309AspfsX4 (16). It was shown that, compared with other pathogenic variants in the APC gene in Russian patients, mutation p.Glu1309AspfsX4 does not result in earlier development of colorectal cancer and polyps. Nineteen mutations were described for the first time. The identified mutations were located between codons 142 and 1492 of the APC gene. This indicates the importance of investigation of all the gene coding exons. Pathogenic variants were observed in 16 of 35 studied relatives of the mutation carriers. All 16 relatives were included in the “risk group” for lifelong clinical monitoring.