Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease
Funding agencies: This study was supported by Canada Excellence Research Chairs program (to Matthew J. Farrer); Canada Research Chairs (to A. Jon Stoessl); the Cundill Foundation (to A. Jon Stoessl and Matthew J. Farrer); Leading Edge Endowment Funds provided by the Province of British Columbia, LifeLabs, and Genome BC, which support the Dr. Donald Rix BC Leadership Chair (to Matthew J. Farrer); the Pacific Parkinson's Research Institute (to Silke Appel-Cresswell); Canadian Institutes of Health Research (to A. Jon Stoessl); the Pacific Alzheimer Research Foundation (to A. Jon Stoessl and Silke Appel-Cresswell); the Regina Curling Classic (to Alex Rajput and Ali H. Rajput); the Royal University Hospital Foundation (to Alex Rajput and Ali H. Rajput); and the Greystone Classic for Parkinson's, Inc. (to Alex Rajput and Ali H. Rajput).
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
Alpha-synuclein plays a central role in the pathophysiology of Parkinson's disease. Three missense mutations in SNCA, the gene encoding alpha-synuclein, as well as genomic multiplications have been identified as causes for autosomal-dominantly inherited Parkinsonism.
Here, we describe a novel missense mutation in exon 4 of SNCA encoding a H50Q substitution in a patient with dopa-responsive Parkinson's disease with a family history of parkinsonism and dementia.
The variant was not observed in public databases or identified in unrelated subjects.
The substitution's evolutionary conservation and protein modeling provide additional support for pathogenicity as the amino acid perturbs the same amphipathic alpha helical structure as the previously described pathogenic mutations. © 2013 Movement Disorder Society