# Identification of a Mosaic BMPR1A Pathogenic Variant in Juvenile Polyposis Syndrome: A Case Study and Its Impact on Cancer Screening

## TL;DR

A rare genetic disorder called Juvenile Polyposis Syndrome was diagnosed in a patient through a mosaic BMPR1A gene variant, impacting cancer screening for the patient and their family.

## Contribution

This case study identifies a mosaic BMPR1A pathogenic variant in a patient with Juvenile Polyposis Syndrome and newly diagnosed colon cancer.

## Key findings

- A BMPR1A pathogenic variant was detected in blood at ~15% allele frequency and in fibroblasts at <10%.
- The patient's history of JPS polyps and variant detection support a diagnosis of JPS due to a mosaic BMPR1A variant.
- The diagnosis influences cancer screening recommendations for the patient and their relatives.

## 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.