# A Novel Missense Variant of BMPR1A in Juvenile Polyposis Syndrome: Assessment of Structural and Functional Alternations

## TL;DR

This paper reports a new BMPR1A gene variant linked to Juvenile Polyposis Syndrome, suggesting it affects protein stability and splicing, offering new insights into the disease's genetic basis.

## Contribution

The study identifies a novel BMPR1A missense variant and proposes its impact on protein structure and function in Juvenile Polyposis Syndrome.

## Key findings

- A novel BMPR1A missense variant (c.355C>T; p.R119C) was identified as pathogenic in Juvenile Polyposis Syndrome.
- The variant is predicted to reduce molecular weight, affecting protein stability and posttranslational modifications.
- The variant may also cause aberrant alternative splicing, contributing to disease mechanisms.

## Abstract

Juvenile polyposis syndrome (JPS) is a rare precancerous condition associated with a high susceptibility to colorectal cancer. The genetic basis of JPS has been reported to lie in germline mutations in BMPR1A or SMAD4, resulting in diverse clinical manifestations and an elusive underlying mechanism. We firstly utilized a 139-gene next-generation sequencing (NGS) panel to detect the germline variants and further employed various prediction tools to assess the pathogenicity and functional alternations. Consequently, we identified a novel pathogenic BMPR1A missense variant (c.355C>T; p.R119C). More importantly, we proposed for the first time that the missense variant would lead to a decrease in molecular weight, potentially associated with reduced protein stability, diminished posttranslational modifications, and aberrant alternative splicing. These findings may provide novel perspectives for further exploration into the role of BMPR1A in JPS development. Also, we hope to encourage clinicians to underscore the importance of genetic testing and analysis in facilitating the diagnosis and treatment of diseases.