Funding agencies: This work was supported by Parkinson's UK (grant number K-0901 awarded to T.F.), the National Institute for Health Research (NIHR) UCL/UCLH Biomedical Research Centres funding Scheme and The Wellcome Trust/Medical Research Council (MRC) funded UK Parkinson's disease consortium.
Genotype and phenotype in Parkinson's disease: Lessons in heterogeneity from deep brain stimulation
Article first published online: 1 JUL 2013
© 2013 The Authors. Movement Disorders published by Wiley on behalf of The 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 28, Issue 10, pages 1370–1375, September 2013
How to Cite
Angeli, A., Mencacci, N. E., Duran, R., Aviles-Olmos, I., Kefalopoulou, Z., Candelario, J., Rusbridge, S., Foley, J., Pradhan, P., Jahanshahi, M., Zrinzo, L., Hariz, M., Wood, N. W., Hardy, J., Limousin, P. and Foltynie, T. (2013), Genotype and phenotype in Parkinson's disease: Lessons in heterogeneity from deep brain stimulation. Mov. Disord., 28: 1370–1375. doi: 10.1002/mds.25535
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: 23 SEP 2013
- Article first published online: 1 JUL 2013
- Manuscript Accepted: 17 APR 2013
- Manuscript Revised: 12 MAR 2013
- Manuscript Received: 1 FEB 2013
- Parkinson's disease;
- deep brain stimulation;
Variation in the genetic risk(s) of developing Parkinson's disease (PD) undoubtedly contributes to the subsequent phenotypic heterogeneity. Although patients with PD who undergo deep brain stimulation (DBS) are a skewed population, they represent a valuable resource for exploring the relationships between heterogeneous phenotypes and PD genetics. In this series, 94 patients who underwent DBS were screened for mutations in the most common genes associated with PD. The consequent genetic subgroups of patients were compared with respect to phenotype, levodopa (l-dopa), and DBS responsiveness. An unprecedented number (29%) of patients tested positive for at least 1 of the currently known PD genes. Patients with Parkin mutations presented at the youngest age but had many years of disease before needing DBS, whereas glucocerebrosidase (GBA) mutation carriers reached the threshold of needing DBS earlier, and developed earlier cognitive impairment after DBS. DBS cohorts include large numbers of gene positive PD patients and can be clinically instructive in the exploration of genotype-phenotype relationships.