@article{01a74f14d3904f0caa52d71d89b45ba8,
title = "Insufficient evidence for pathogenicity of SNCA His50Gln (H50Q) in Parkinson's disease",
abstract = "SNCA missense mutations are a rare cause of autosomal dominant Parkinson's disease (PD). To date, 6 missense mutations in SNCA have been nominated as causal. Here, we assess the frequency of these 6 mutations in public population databases and PD case-control data sets to determine their true pathogenicity. We found that 1 of the 6 reported SNCA mutations, His50Gln, was consistently identified in large population databases, and no enrichment was evident in PD cases compared to controls. These results suggest that His50Gln is probably not a pathogenic variant. This information is important to provide counseling for His50Gln carriers and has implications for the interpretation of His50Gln α-synuclein functional investigations.",
keywords = "H50Q, His50Gln, Parkinson's disease, SNCA",
author = "Cornelis Blauwendraat and Kia, {Demis A.} and Lasse Pihlstr{\o}m and Ziv Gan-Or and Suzanne Lesage and Gibbs, {J. Raphael} and Jinhui Ding and Alcalay, {Roy N.} and Sharon Hassin-Baer and Pittman, {Alan M.} and Janet Brooks and Connor Edsall and Chung, {Sun Ju} and Stefano Goldwurm and Mathias Toft and Claudia Schulte and Dena Hernandez and Singleton, {Andrew B.} and Nalls, {Mike A.} and Alexis Brice and Scholz, {Sonja W.} and Wood, {Nicholas W.} and Noyce, {Alastair J.} and Arianna Tucci and Gavin Charlesworth and Manuela Tan and Henry Houlden and Morris, {Huw R.} and Helene Plun-Favreau and Peter Holmans and John Hardy and Bras, {Jose M.} and John Quinn and Mok, {Kin Y.} and Kimberley Billingsley and Patrick Lewis and Rita Guerreiro and Ruth Lovering and Ogalla, {Raquel Duran} and Lea R{\textquoteright}bibo and Mina Ryten and Valentina Escott-Price and Viorica Chelban and Thomas Foltynie and Sheerin, {Una Marie} and Nigel Williams and Fabrice Danjou and Corvol, {Jean Christophe} and Maria Martinez and Rejko Kr{\"u}ger and {International Parkinson's Disease Genomics Consortium (IPDGC), COURAGE-PD Consortium}",
note = "Funding Information: The authors would like to thank all members of the IPDGC ( http://pdgenetics.org/partners ) and COURAGE-PD consortia for proving data, support, and comments. This work was supported (in part) by the Intramural Research Program of the National Institutes of Health (National Institute of Neurological Disorders and Stroke, National Institute on Aging; projects 1ZIA-NS003154-2 and Z01-AG000949) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. Data used in the preparation of this article were obtained from the Parkinson's Progression Markers Initiative (PPMI) database ( www.ppmi-info.org/data ). For up-to-date information on the study, visit www.ppmi-info.org . Funding Information: Dr. Mike A. Nalls' participation is supported by a consulting contract between Data Tecnica International LLC and the National Institute on Aging, NIH, Bethesda, MD, USA. He also consults for Illumina Inc, the Michael J. Fox Foundation, and University of California Healthcare. Funding Information: PPMI, a public-private partnership, is funded by the Michael J. Fox Foundation for Parkinson's Research and funding partners, including AbbVie, Avid, Biogen, Bristol-Myers Squibb, Covance, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Roche, Servier, Teva, UCB, and Golub Capital. The study on the cohort from McGill University was financially supported by the Michael J. Fox Foundation and by the Canadian Consortium on Neurodegeneration in Aging (CCNA). The study on the cohort from France was performed by the French Parkinson's Disease Genetics Study Group (PDG) and supported by the France Parkinson's Association. Also we thank Dr. Thibaud Lebouvier as the neurologist who examined the homozygous His50Gln SNCA patient. Columbia University Spot cohort was funded by the NIH (K02NS080915) and the Parkinson's Disease Foundation. We thank Guy Rouleau, Jennifer Ruskey, Sandra B Laurent, Pascale Hince, Dan Spiegelman, Alexandre Dionne-Laporte, Helene Catoire, Cynthia Bourassa, Pierre Provencher, Cathy Mirarchi, and Vessela Zaharieva for their assistance. We thank the Quebec Parkinson's Network and its members ( http://rpq-qpn.ca/ ) for their collaboration. COURAGE-PD (COmprehensive Unbiased Risk factor Assessment for Genetics and Environment in Parkinson's Disease) is a transnational project funded by the EU Joint Programme–Neurodegenerative Disease Research (JPND). Publisher Copyright: {\textcopyright} 2017",
year = "2018",
month = apr,
day = "1",
doi = "10.1016/j.neurobiolaging.2017.12.012",
language = "English",
volume = "64",
pages = "159.e5--159.e8",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
}