Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome associated with mutation in the adenomatous polyposis coli (APC) gene, a tumour suppressor located on chromosome 5q21. Attenuated familial adenomatous polyposis (AFAP) is a variant associated with fewer and later onset of colon polyps. AFAP-associated APC mutations have largely been found before codon 157, in exon 9 or after codon 1595. We present the case of a 44-year-old man incidentally found to have numerous gastric polyps during bariatric surgery, with innumerable polyps in the remaining part of the stomach and the entire colon, with rectal sparing, consistent with AFAP phenotype. Genetic testing demonstrated the c.7682dup (p.Ser2562Lysfs*21) variant in exon 15 of APC. This represents a previously undescribed APC mutation. This mutation likely yields end-binding protein 1 and human disc large binding protein inactivation, causing cell cycle microtubule dysregulation and tumour suppressor inactivation. Through loss of these regulatory mechanisms, this mutation is associated with AFAP phenotype. The patient was treated surgically and is doing well.
Identification of 5 novel germline APC mutations and characterization of clinical phenotypes in Japanese patients with classical and attenuated familial adenomatous polyposis
