Objective: To verify the reported association of Parkinson’s disease(PD) with Chromosome 22q11.2 Deletion Syndrome(22q11.2DS) in series of large, independent idiopathic PD case-control studies.

Background: PD is the second most common neurodegenerative disease. Microdeletions at chromosome 22q11.2 (22qDel) are the most frequent known interstitial deletion found in humans and have been associated with a heterogeneous range of clinical syndromes which are collectively termed the 22q11.2DS. Previous case reports and one case series have suggested this deletion may be associated with PD. There is no data from large PD cohorts investigating the potential role of 22qDel increasing risk to PD. In this study we screened a series of large, independent PD case-control studies for deletions at 22q11.2.

Methods: Data on deletions spanning the 22q11.2 locus were available from four independent case-control PD datasets from the UK, Netherlands, US, and the International PD Genomics Consortium, all of which were independent of the original reports of 22q11.2DS. This resulted in the inclusion of array-based CNV data from a total of 9,387 PD cases and 13,863 controls. Case-control association analysis was performed comparing the proportion of 22qDel found. Clinical details of the positive cases were retrieved from the records.

Results: We identified a significant excess of rare deletions spanning the 22q11.2 locus in PD cases. Among the 4 datasets, eight deletions were found in PD cases and zero in controls (frequency = 0.09% and 0% respectively, p=0.00056). Deletions at 22q11.2 were correlated with disease age at onset (p=6.53E-5) and were particularly enriched in patients with early-onset PD (using cut off age at < 45; frequency = 0.49%; p=1.59E-6).

Conclusions: This study confirms that chromosome 22q11.2 deletions are associated with an increased prevalence of PD, and this is especially noticeable for the early-onset form of the disease. This 22qDel has a proven strong association with schizophrenia & psychiatric symptoms, cardiovascular, craniofacial & other morphometric changes, immunological and other associated diseases. Clinicians should be alert to the possibility of 22qDel for PD cases that have early presentation and/or features associated with the 22q11.2DS. Carriers of this 22qDel are prone to multiple other potential co-morbidities and clinicians should actively probe for these co-morbidities when managing 22qDel-related PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/deletions-at-22q11-2-in-idiopathic-parkinsons-disease-a-combined-analysis-of-gwas-data/