Identification of a Mosaic Pathogenic Variant in Juvenile Polyposis Syndrome: A Case Study and Its Impact on Cancer Screening.

Juvenile polyposis syndrome (JPS) (MIM: 174900) is a rare genetic disorder characterized by multiple benign, hamartomatous polyps, and an increased risk for colorectal and gastric cancer. It is caused by pathogenic variants in and . We present the findings of a mosaic pathogenic variant in a 57-year-old patient with newly diagnosed colon cancer and a history of polyps, which were later discovered to be JPS polyps. The variant was first identified in a blood sample at approximately 15% allele frequency. Subsequent genetic testing performed on gDNA from cultured fibroblasts found this variant to be present at very low levels (< 10%). The finding of this variant in two sample types, as well as the history of JPS polyps, supports a diagnosis of JPS due to a mosaic pathogenic variant. This diagnosis affects cancer screening recommendations for our patient and his relatives. Our case highlights the need for recognition and workup of potentially mosaic cases and for universal germline genetic testing for patients with colorectal cancer.