Clinical and Molecular Characteristics of a Female Familial Adenomatous Polyposis Patient With Adenomatous Polyposis Coli (APC) p.Arg554* Variant and the Value of Screening Her Relatives.

Familial adenomatous polyposis (FAP) accounts for 1% of all colorectal cancer cases and is an autosomal dominant trait with varying expression of the phenotype caused by a disease-causing variant in the adenomatous polyposis coli ( gene. This study aims to investigate the molecular characteristics of a patient with FAP, along with its clinical presentation, diagnosis, and treatment plan. We report a case of a 32-year-old female with a maternal history of FAP who was first diagnosed with stage IV rectal cancer. Next-generation sequencing-based genetic diagnostics using a panel of 36 genes linked to hereditary cancer predisposition revealed a maternally inherited pathogenic variant c.1660C>T (p.Arg554*). Variant-specific testing in the patient's first-degree relative demonstrated that her asymptomatic younger sister also carried this variant. A colonoscopy revealed the existence of early colonic polyps in the transverse colon to the rectum, which had spared the ascending colon. This study demonstrates that identifying the disease-causing gene in the proband could be beneficial in providing ongoing genetic counseling to family members. The results of the study can be utilized to identify first-degree relatives who are susceptible to hereditary cancer. This will enable the relatives to modify their lifestyle and reduce their cancer risk, resulting in increased surveillance, monitoring, and treatment planning.