# Paternal UPD (15) With Disease-Causing Mutation and Small Supernumerary Ring Chromosome 15: A Case Report

## TL;DR

A patient with Bartter syndrome had a rare genetic condition involving paternal UPD and a ring chromosome, revealing a new cause for the disease.

## Contribution

This case highlights a novel etiology of Bartter syndrome involving paternal UPD and a ring chromosome.

## Key findings

- Paternal UPD of chromosome 15 unmasked a pathogenic SLC12A1 variant, causing Bartter syndrome Type 1.
- A maternally derived ring chromosome 15 contributed to nondisjunction and UPD.
- Trisomy rescue events led to two distinct cell lines and disease manifestation.

## Abstract

Uniparental disomy (UPD) constitutes an unconventional mode of inheritance that disrupts the typical biparental genetic contribution and may result in phenotypic abnormalities. This report centers on a patient diagnosed with Bartter syndrome Type 1, attributed to a homozygous pathogenic variant in SLC12A1 unmasked by mosaic paternal UPD of chromosome 15. We hypothesize that this pattern (or constellation) emerged from a trisomy rescue event, resulting in two distinct cell lines. Concurrently, the unmasking of a pathogenic paternal SLC12A1 variant by trisomy rescue resulted in the manifestation of Bartter syndrome Type 1. The maternally derived ring chromosome 15 and its impact on nondisjunction and UPD elucidate a unique etiology of Bartter syndrome. Furthermore, the presence of a pathogenic paternal SLC12A1 variant underscores the pivotal role of trisomic rescue and paternal UPD in unveiling a recessive variant.