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

Choate, Lauren A.; Hoffman, Francis; Newman, Jessica H.; Runke, Cassandra; Webley, Matthew; Hoppman, Nicole L.; Thorland, Erik C.

doi:10.3390/genes16060630

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

by

Lauren A. Choate

^1,2,*

,

Francis Hoffman

¹,

Jessica H. Newman

¹,

Cassandra Runke

¹

,

Matthew Webley

¹,

Nicole L. Hoppman

¹ and

Erik C. Thorland

^1,*

¹

Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA

²

Division of Cytogenetics, Center for Advanced Molecular Diagnostics, Department of Pathology, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02115, USA

^*

Authors to whom correspondence should be addressed.

Genes 2025, 16(6), 630; https://doi.org/10.3390/genes16060630 (registering DOI)

Submission received: 8 May 2025 / Revised: 16 May 2025 / Accepted: 23 May 2025 / Published: 24 May 2025

(This article belongs to the Special Issue Clinical Cytogenetics: Current Advances and Future Perspectives)

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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.

Keywords: PRKN; mosaicism; phase determination; chromosomal microarray

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MDPI and ACS Style

Choate, L.A.; Hoffman, F.; Newman, J.H.; Runke, C.; Webley, M.; Hoppman, N.L.; Thorland, E.C. Phase Determination and Demonstration of Parental Mosaicism of Intragenic PRKN Deletions Initially Identified by Chromosomal Microarray Analysis. Genes 2025, 16, 630. https://doi.org/10.3390/genes16060630

AMA Style

Choate LA, Hoffman F, Newman JH, Runke C, Webley M, Hoppman NL, Thorland EC. Phase Determination and Demonstration of Parental Mosaicism of Intragenic PRKN Deletions Initially Identified by Chromosomal Microarray Analysis. Genes. 2025; 16(6):630. https://doi.org/10.3390/genes16060630

Chicago/Turabian Style

Choate, Lauren A., Francis Hoffman, Jessica H. Newman, Cassandra Runke, Matthew Webley, Nicole L. Hoppman, and Erik C. Thorland. 2025. "Phase Determination and Demonstration of Parental Mosaicism of Intragenic PRKN Deletions Initially Identified by Chromosomal Microarray Analysis" Genes 16, no. 6: 630. https://doi.org/10.3390/genes16060630

APA Style

Choate, L. A., Hoffman, F., Newman, J. H., Runke, C., Webley, M., Hoppman, N. L., & Thorland, E. C. (2025). Phase Determination and Demonstration of Parental Mosaicism of Intragenic PRKN Deletions Initially Identified by Chromosomal Microarray Analysis. Genes, 16(6), 630. https://doi.org/10.3390/genes16060630

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

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