Funding agencies: This study was supported by grants from Parkinson's UK (Innovation Grant K-1111), and the Wellcome Trust / MRC joint call in Neurodegeneration strategic award (WT089698). DNA extraction work was partly undertaken at University College London Hospitals, University College London, who received a proportion of funding from the Department of Health's National Institute for Health Research Biomedical Research Centres funding. Tissue samples and associated clinical and neuropathological data were supplied amongst others by the Parkinson's UK Tissue Bank, funded by Parkinson's UK, a charity registered in England and Wales (258197) and in Scotland (SC037554).
Analysis of Parkinson's disease brain–derived DNA for alpha-synuclein coding somatic mutations
Article first published online: 21 APR 2014
© 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 29, Issue 8, pages 1060–1064, July 2014
How to Cite
Proukakis, C., Shoaee, M., Morris, J., Brier, T., Kara, E., Sheerin, U.-M., Charlesworth, G., Tolosa, E., Houlden, H., Wood, N. W. and Schapira, A. H. (2014), Analysis of Parkinson's disease brain–derived DNA for alpha-synuclein coding somatic mutations. Mov. Disord., 29: 1060–1064. doi: 10.1002/mds.25883
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.
- Issue published online: 17 JUL 2014
- Article first published online: 21 APR 2014
- Manuscript Accepted: 6 MAR 2014
- Manuscript Revised: 16 FEB 2014
- Manuscript Received: 14 DEC 2013
- somatic mutation;
- etiology of Parkinson's disease
Although alpha-synuclein (SNCA) is crucial to the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), mutations in the gene appear to be rare. We have recently hypothesized that somatic mutations in early development could contribute to PD.
Expanding on our recent negative small study, we used high-resolution melting (HRM) analysis to screen SNCA coding exons for somatic point mutations in DNA from 539 PD and DLB cerebellar samples, with two additional regions (frontal cortex, substantia nigra) for 20 PD cases. We used artificial mosaics to determine sensitivity where possible.
We did not detect any evidence of somatic coding mutations. Three cases were heterozygous for known silent polymorphisms. The protocol we used was sensitive enough to detect 5% to 10% mutant DNA.
Using DNA predominantly from cerebellum, but also from frontal cortex and substantia nigra (n = 20 each), we have not detected any somatic coding SNCA point mutations. © 2014 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.