Identification of FUS p.R377W in essential tremor
Article first published online: 3 JUL 2013
© 2013 The Author(s) European Journal of Neurology © 2013 EFNS
European Journal of Neurology
Volume 21, Issue 2, pages 361–363, February 2014
How to Cite
Rajput, A., Rajput, A. H., Rajput, M. L., Encarnacion, M., Bernales, C. Q., Ross, J. P., Farrer, M. J. and Vilariño-Güell, C. (2014), Identification of FUS p.R377W in essential tremor. European Journal of Neurology, 21: 361–363. doi: 10.1111/ene.12231
- Issue published online: 13 JAN 2014
- Article first published online: 3 JUL 2013
- Manuscript Accepted: 5 JUN 2013
- Manuscript Received: 7 MAY 2013
- Canada Research Chair
- Excellence Research Chairs program
- Leading Edge Endowment Funds
- Regina Curling Classic for Parkinson Research
- Greystone Golf Classic for Parkinson's and Royal University Hospital Foundation
- amyotrophic lateral sclerosis;
- essential tremor;
- FUS ;
Background and purpose
Exome sequencing analysis has recently identified a nonsense mutation in fused in sarcoma (FUS) segregating with essential tremor (ET) within a large French-Canadian family. Further characterization of FUS resulted in the identification of additional mutations in ET patients; however, their pathogenicity still remains to be confirmed. The role of FUS in an independent cohort of ET patients from Canada was evaluated.
The entire coding sequence of FUS in 217 patients diagnosed with ET was analyzed and two missense variants in 219 healthy controls were genotyped by Sanger sequencing.
Sequencing of FUS identified a previously reported non-pathogenic mutation p.G174_G175del in one ET patient and two healthy controls, and a novel p.R377W in one patient with family history of disease. This mutation is highly conserved and strongly predicted to be damaging by in silico analysis.
This study has identified a novel FUS p.R377W substitution in ET patients. Additional genotyping studies in a large number of ET patients and controls are necessary to conclusively define its pathogenicity.