# Phase Determination and Demonstration of Parental Mosaicism of Intragenic PRKN Deletions Initially Identified by Chromosomal Microarray Analysis

## TL;DR

This paper describes a case where genetic testing revealed two PRKN gene deletions in a patient with early-onset Parkinson disease, showing the importance of advanced techniques to confirm inheritance patterns and parental mosaicism.

## Contribution

The study demonstrates the use of combined genetic methods to identify parental mosaicism and phase deletions in PRKN, improving diagnostic accuracy for ARJP.

## Key findings

- Low-level maternal mosaicism was detected for the de novo PRKN deletion.
- The deletions were confirmed to be in trans, supporting a diagnosis of autosomal recessive juvenile Parkinson disease.
- Combining microarray, long-range PCR, and Sanger sequencing proved effective for phase determination.

## Abstract

Background: Autosomal recessive juvenile Parkinson disease (ARJP) is an early-onset neurodegenerative disorder characterized by Parkinsonian motor symptoms with slow progression and preserved cognition. Biallelic pathogenic variants within the PRKN gene are associated with ARJP. Among PRKN pathogenic variants, deletions are a frequent occurrence and may be identified through chromosomal microarray testing. Methods: Here we present a case with two intragenic PRKN deletions initially identified as a secondary finding using chromosomal microarray. One deletion was paternally inherited and the second initially appeared to be de novo. In addition to microarray which initially identified the two deletions, long-range GAP-PCR and Sanger sequencing were used to further characterize the de novo deletion and phase of the deletions. Results: Molecular characterization of the apparently de novo deletion demonstrated low-level maternal mosaicism of this deletion, thus proving that these deletions are in trans in the proband, yielding a diagnosis of autosomal recessive juvenile Parkinson disease. Conclusions: This case highlights the utility of a diagnostic approach combining microarray, long-range PCR, and Sanger sequencing to establish the phase and confirm biallelic PRKN deletions in a patient with ARJP. Furthermore, these findings highlight the importance of investigating the possibility of parental mosaicism to determine the phase of autosomal recessive variants and establish accurate recurrence risks.