Investigation of the functional significance of variant c.423-6A>G in the APC gene in a patient with familial adenomatous polyposis

Abstract

Up to 1% of all colorectal cancers appear as a result of familial adenomatous polyposis. This hereditary syndrome in most cases is driven by APC gene germline mutations. Around 85% of mutations are small deletions/insertions and nonsence mutations, while other 15% are large deletions, missence and splice site mutations. Meanwhile, functional significance of some of missence mutations and intronic variants of APC gene is not described. We determined pathogenic significance of a previously not described c.423-6A>G variant of APC gene in a patient with familial adenomatous polyposis. We analyzed mutation changes on mRNA level revealing changes of transcript as a result of disturbed splicing process. Data strongly suggests that c.423-6A>G variant of APC gene is a pathogenic mutation.