Identification of a Mosaic BMPR1A Pathogenic Variant in Juvenile Polyposis Syndrome: A Case Study and Its Impact on
Kara Rogen1, Lisa Boardman2, Megan Bird2
1Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA.
Insights
Juvenile polyposis syndrome (JPS) can be caused by mosaic BMPR1A variants, as seen in a colon cancer patient. Early recognition of mosaic JPS is crucial for cancer screening and genetic testing recommendations.
Area of Science:
- Genetics
- Oncology
- Gastroenterology
Background:
- Juvenile polyposis syndrome (JPS) is a rare genetic disorder linked to increased cancer risk.
- JPS is typically caused by pathogenic variants in SMAD4 or BMPR1A.
- Mosaicism, where a variant is present in some cells but not others, can complicate genetic diagnoses.
Abstract:
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 SMAD4 and BMPR1A. We present the findings of a mosaic BMPR1A 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 BMPR1A variant in two sample types, as well as the history of JPS polyps, supports a diagnosis of JPS due to a mosaic BMPR1A 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.
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