• Kin Y Mok, Una Sheerin, Javier Simón-Sánchez, Afnan Salaka, Lucy Chester, Valentina Escott-Price, Kiran Mantripragada, Karen M Doherty, Alastair J Noyce, Niccolo E Mencacci, Steven J Lubbe, International Parkinson's Disease Genomics Consortium (IPDGC), Caroline H Williams-Gray, Roger A Barker, Karin D van Dijk, Henk W Berendse, Peter Heutink, Jean-Christophe Corvol, Florence Cormier, Suzanne Lesage, Alexis Brice, Kathrin Brockmann, Claudia Schulte, Thomas Gasser, Thomas Foltynie, Patricia Limousin, Karen E Morrison, Carl E Clarke, Stephen Sawcer, Tom T Warner, Andrew J Lees, Huw R Morris, Mike A Nalls, Andrew B Singleton, John Hardy, Andrey Y Abramov, Vincent Plagnol, Nigel M Williams, and Nicholas W Wood.
• Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK; Division of Life Science, Hong Kong University of Science and Technology, Hong Kong Special Administrative Region, China.
• Lancet Neurol. 2016 May 1; 15 (6): 585596585-96.

BackgroundParkinson's disease has been reported in a small number of patients with chromosome 22q11.2 deletion syndrome. In this study, we screened a series of large, independent Parkinson's disease case-control studies for deletions at 22q11.2.MethodsWe used data on deletions spanning the 22q11.2 locus from four independent case-control Parkinson's disease studies (UK Wellcome Trust Case Control Consortium 2, Dutch Parkinson's Disease Genetics Consortium, US National Institute on Aging, and International Parkinson's Disease Genomics Consortium studies), which were independent of the original reports of chromosome 22q11.2 deletion syndrome. We did case-control association analysis to compare the proportion of 22q11.2 deletions found, using the Fisher's exact test for the independent case-control studies and the Mantel-Haenszel test for the meta-analyses. We retrieved clinical details of patients with Parkinson's disease who had 22q11.2 deletions from the medical records of these patients.FindingsWe included array-based copy number variation data from 9387 patients with Parkinson's disease and 13 863 controls. Eight patients with Parkinson's disease and none of the controls had 22q11.2 deletions (p=0·00082). In the 8451 patients for whom age at onset data were available, deletions at 22q11.2 were associated with Parkinson's disease age at onset (Mann-Whitney U test p=0·001). Age at onset of Parkinson's disease was lower in patients carrying a 22q11.2 deletion (median 37 years, 95% CI 32·0-55·5; mean 42·1 years [SD 11·9]) than in those who did not carry a deletion (median 61 years, 95% CI 60·5-61·0; mean 60·3 years [SD 12·8]). A 22q11.2 deletion was present in more patients with early-onset (p<0·0001) and late-onset Parkinson's disease (p=0·016) than in controls, and in more patients with early-onset than late-onset Parkinson's disease (p=0·005).InterpretationClinicians should be alert to the possibility of 22q11.2 deletions in patients with Parkinson's disease who have early presentation or features associated with the chromosome 22q11.2 deletion syndrome, or both.FundingUK Medical Research Council, UK Wellcome Trust, Parkinson's UK, Patrick Berthoud Trust, National Institutes of Health, "Investissements d'Avenir" ANR-10-IAIHU-06, Dutch Parkinson Foundation (Parkinson Vereniging), Neuroscience Campus Amsterdam, National Institute for Health Research, National Institute on Aging, National Institutes of Health.Copyright © 2016 Mok et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

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