A rare upstream regulatory region mutation in APC presenting as classical familial adenomatous polyposis: A case report and literature review

Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary syndrome primarily characterized by extensive colorectal adenomatous polyps and a substantially increased risk of colorectal cancer (CRC). FAP typically results from germline mutations within the coding regions of the adenomatous polyposis coli (APC) gene. However, mutations involving noncoding regulatory regions, particularly APC promoter 1B, have recently been identified. The present study reports a rare pathogenic variant (c.-30266G>A) located far upstream from the typical promoter 1B region in a 63-year-old patient presenting with classical features of FAP, including extensive colorectal polyposis and CRC. Notably, despite this variant's known association with gastric adenocarcinoma and proximal polyposis of the stomach, the patient exhibited no gastric involvement. Cascade genetic testing identified the same variant in the patient's daughter, who remains asymptomatic. Overall, this case highlights the phenotypic variability and diagnostic challenges associated with noncoding APC mutations and underscores the importance of including distal regulatory regions in genetic testing panels for patients with FAP lacking coding-region mutations. Further research is required to elucidate the exact molecular mechanisms and broader clinical implications of these noncoding variants.