Identification of large deletions in the APC gene in Russian patients with familial adenomatous polyposis

Alexey Tsukanov, Viktoria Zabnenkova, Vitaliy Shubin,  Dmitry Pikunov, Tatyana Savelyeva, Alexander Kuzminov, Sergey Frolov, Alexander Polyakov, Yuriy Shelygin

Abstract:

Familial adenomatous polyposis (FAP) is a hereditary syndrome characterized by the presence of multiple adenomatous polyps in the colon. The main cause of the disease is a germline mutation in the APC gene. Here we report 4 unrelated FAP patients with different large deletions in the APC gene detected by Multiplex Ligation-dependent Probe Amplification (MLPA) method: deletion of exons 7-15, deletion of promoters B, A, and 5’-UTR region and deletion of promoter B (in 2 patients). The deletion of promoters B, A, and 5’-UTR was not described in the literature earlier, so we report it for the first time. In 2 families with promoter B deletion, we could identify the tendency for decreasing the age of disease manifestation in each next generation, in contrast to the previous one. The incidence of large deletions in APC among Russian patients with FAP reached 4.8% and our finding suggests the need to study this gene by MLPA in “no mutation patients” after Sanger’s sequencing.