Funding agencies: This study as well as the recruitment of the case sample was funded by in-house institutional funding from Technische Universität München and Helmholtz Zentrum München, Munich, Germany. Recruitment of the control cohort was supported by institutional funding from Helmholtz Zentrum München, Munich, Germany, and government funding from the German Bundesministerium für Bildung und Forschung (BMBF, 03.2007-02.2011 FKZ 01ET0713).
Rare sequence variants in ANO3 and GNAL in a primary torsion dystonia series and controls
Version of Record online: 22 OCT 2013
Copyright © 2013 Movement Disorder Society
Volume 29, Issue 1, pages 143–147, January 2014
How to Cite
Zech, M., Gross, N., Jochim, A., Castrop, F., Kaffe, M., Dresel, C., Lichtner, P., Peters, A., Gieger, C., Meitinger, T., Haslinger, B. and Winkelmann, J. (2014), Rare sequence variants in ANO3 and GNAL in a primary torsion dystonia series and controls. Mov. Disord., 29: 143–147. doi: 10.1002/mds.25715
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 online: 23 JAN 2014
- Version of Record online: 22 OCT 2013
- Manuscript Accepted: 11 SEP 2013
- Manuscript Revised: 26 AUG 2013
- Manuscript Received: 5 JUN 2013
- rare variants
Rare autosomal-dominant mutations in ANO3 and GNAL have been recently shown to represent novel genetic factors underlying primary torsion dystonia (PTD) with predominantly craniocervical involvement.
We used high-resolution melting to screen all exons of ANO3 and GNAL for rare sequence variants in a population of 342 German individuals with mainly sporadic PTD and 376 general population controls.
We identified 2 novel missense variants in ANO3 (p.Ile833Val and p.Gly973Arg) and 1 novel missense variant in GNAL (p.Val146Met) in three different nonfamilial cases. Variant carriers presented with adult-onset dystonia involving the neck and/or face. In controls, 3 rare ANO3 missense variants (p.Tyr235Cys, p.Asn256Ser, and p.Pro893Leu) but no rare nonsynonymous GNAL variants were present.
GNAL variants seem to be a rare cause of PTD in our mainly sporadic German sample. Low frequency missense variants in ANO3 occur in both cases and controls, warranting further assessment of this gene in PTD pathogenesis. © 2013 International Parkinson and Movement Disorder Society