Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease

Authors

  • Silke Appel-Cresswell MD,

    Corresponding author
    1. Department of Medicine (Neurology), Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada
    • Correspondence to: Dr. Silke Appel-Cresswell, Pacific Parkinson's Research Centre, Department of Medicine (Neurology), University of British Columbia, Vancouver, BC, Canada, V6T 2B5; silkec@mail.ubc.ca

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  • Carles Vilarino-Guell PhD,

    1. Department of Medical Genetics, Centre for Applied Neurogenetics, University of British Columbia, Vancouver, British Columbia, Canada
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  • Mary Encarnacion BSc,

    1. Department of Medical Genetics, Centre for Applied Neurogenetics, University of British Columbia, Vancouver, British Columbia, Canada
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  • Holly Sherman BSc,

    1. Department of Medical Genetics, Centre for Applied Neurogenetics, University of British Columbia, Vancouver, British Columbia, Canada
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  • Irene Yu MSc,

    1. Department of Medical Genetics, Centre for Applied Neurogenetics, University of British Columbia, Vancouver, British Columbia, Canada
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  • Brinda Shah MSc,

    1. Department of Medical Genetics, Centre for Applied Neurogenetics, University of British Columbia, Vancouver, British Columbia, Canada
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  • David Weir MSc,

    1. Department of Medicine (Neurology), Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada
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  • Christina Thompson BSc,

    1. Department of Medical Genetics, Centre for Applied Neurogenetics, University of British Columbia, Vancouver, British Columbia, Canada
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  • Chelsea Szu-Tu MSc,

    1. Department of Medical Genetics, Centre for Applied Neurogenetics, University of British Columbia, Vancouver, British Columbia, Canada
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  • Joanne Trinh BSc,

    1. Department of Medical Genetics, Centre for Applied Neurogenetics, University of British Columbia, Vancouver, British Columbia, Canada
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  • Jan O. Aasly MD,

    1. Department of Neurology, St. Olav's Hospital, Trondheim, Norway
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  • Alex Rajput MD,

    1. Division of Neurology, University of Saskatchewan and Saskatoon Health Region, Saskatoon, Saskatchewan, Canada
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  • Ali H. Rajput MD,

    1. Division of Neurology, University of Saskatchewan and Saskatoon Health Region, Saskatoon, Saskatchewan, Canada
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  • A. Jon Stoessl MD,

    1. Department of Medicine (Neurology), Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada
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  • Matthew J. Farrer PhD

    1. Department of Medicine (Neurology), Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada
    2. Department of Medical Genetics, Centre for Applied Neurogenetics, University of British Columbia, Vancouver, British Columbia, Canada
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  • 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.

ABSTRACT

Background

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.

Methods

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.

Results

The variant was not observed in public databases or identified in unrelated subjects.

Conclusions

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

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