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.
| Original language | English |
|---|---|
| Journal | Neurobiology of Aging |
| Volume | 64 |
| Pages (from-to) | 159.e5-159.e8 |
| ISSN | 0197-4580 |
| DOIs | |
| Publication status | Published - 01.04.2018 |
Funding
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. 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 . 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).
Research Areas and Centers
- Research Area: Medical Genetics
