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. 2023 Feb 27;14(3):600.
doi: 10.3390/genes14030600.

PARK2 Microdeletion or Duplications Have Been Implicated in Different Neurological Disorders Including Early Onset Parkinson Disease

Ausaf Ahmad  1 , Dingani Nkosi  1 , Mohammed A Iqbal  1
Affiliations

PARK2 Microdeletion or Duplications Have Been Implicated in Different Neurological Disorders Including Early Onset Parkinson Disease

Ausaf Ahmad et al. Genes (Basel). .

Abstract

The PARK2 gene is located on 6q26, encodes ubiquitin-E3- ligase, and is a transcriptional repressor of p53. It contains 12 exons. PARK2 copy number variants has been reported in various types of neurodevelopmental disorders, namely schizophrenia, Parkinson's disease (PD), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). In this retrospective study, nine cases (five with microdeletion and four with microduplication) are reported with 6q26 deletion disrupting the PARK2 gene. Microdeletion sizes ranged between 215 Kb and 356 Kb, and duplication between 279 Kb and 726 Kb. These were present within the exons 7-10. Family follow up with FISH probes revealed paternal inheritance in two cases, maternal in two cases, and de novo origin in one case. Our results support previous studies showing that patients with PARK2 CNVs involving exons 5-12 might be more deleterious and cause a unique syndrome. Comprehensive analysis of additional case studies is needed to have a full characterization of this neurological disorder syndrome.

Keywords: PARK2; array CGH; microdeletion; microduplication; neurodevelopmental disorder.

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Conflict of interest statement

The authors declare no conflict of interest. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. The use of trademarks is for identification purposes only and does not imply endorsement by the U.S. Department of Health and Human Services.

Figures

Figure 1
Figure 1
(A) Schematic presentation of cDNA of the parkin (PARK2) gene exons and (B) Structure of full-length Parkin (PDB 5C1Z). Note: The protein structure was downloaded from RCSB PDB: Homepage and Cn3D macromolecular structure viewer (Cn3D Home Page (nih.gov) was used for preparation of schematic figure. The presentation is not to the scale.
Figure 2
Figure 2
FISH images from eight of the nine patients demonstrating duplication or deletion within the 6q26 region.
Figure 3
Figure 3
Schematic of chromosome 6 and comparison of the nine cases with deletion/duplication of 6q26 locus (see Table 2).
See this image and copyright information in PMC

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