News Release

A new gene identified for restless legs syndrome

Peer-Reviewed Publication


People suffering from restless legs syndrome (RLS) experience unpleasant sensations in the legs at night for which the only remedy is movement. Now, an international consortium from Europe, Canada and the US has identified new genetic risk factors for the disease. Carriers of these risk variants have an increased likelihood of developing RLS. This finding, which will be published on July 14th in the open-access journal PLoS Genetics, presents new opportunities for future research of this disorder.

RLS is amongst the most common neurological diseases. Patients suffer from an urge to move and paresthesia – tingling, prickling and numbness – in the legs, occurring mainly in the evening or at night when the body is at rest. These sensations may only be relieved by moving or walking around, which may result in severe sleeping disorders, chronic sleep loss and daytime fatigue. In severe cases the disease can lead to depression and social isolation. The frequency of RLS increases with age: up to ten per cent of those above 65 years of age are affected, albeit in very different forms. Children can, however, also contract the disease.

For many years, the Institute of Human Genetics, Helmholtz Zentrum Munich and the Technische Universität Munich have been researching the origin of RLS, aiming to improve diagnostics and the treatment of patients. The consortium, led by Professor Juliane Winkelmann, has investigated more than 4,867 RLS patients and 7,280 control patients. The researchers analysed genetic sequence variants (SNPs) distributed over the entire genome and discovered two new genetic regions which play a role in the development of RLS. One of these regions is within a gene involved in regulating brain activity, TOX3. While it is known that increased TOX3 protein protects neuronal cells from cell death, the precise connection between TOX3 and RLS is as yet unknown.

These findings enable further investigation into the underlying mechanisms, which is prerequisite to the development of new treatments.


FINANCIAL DISCLOSURE: The replication phase was supported by a grant from the US RLS Foundation. Part of this work was financed by the National Genome Research Network (NGFN). The KORA study group consists of H-E Wichmann (speaker), R Holle, J John, T Illig, C Meisinger, A Peters, and their coworkers, who are responsible for the design and conduction of the KORA studies. The KORA research platform (KORA, Cooperative Research in the Region of Augsburg) was initiated and financed by the Helmholtz Zentrum Mu¨ nchen, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria. The collection of sociodemographic and clinical data in the Dortmund Health Study was supported by the German Migraine & Headache Society (DMKG) and by unrestricted grants of equal share from Astra Zeneca, Berlin Chemie, Boots Healthcare, Glaxo-Smith-Kline, McNeil Pharma (former Woelm Pharma), MSD Sharp & Dohme, and Pfizer to the University of Muenster. Blood collection in the Dortmund Health Study was done through funds from the Institute of Epidemiology and Social Medicine, University of Muenster. Data collection in the COR-Study was supported by unrestricted grants of the German RLS Society (Deutsche Restless Legs Vereinigung e.V.) and Axxonis Pharma, Boehringer Ingelheim Pharma, Mundipharma Research, Roche Pharma, and UCB to the University of Muenster. CG Bachmann was supported by grants of the German RLS Society, Deutsche Restless Legs Vereinigung, e.V. H Prokisch and T Meitinger were supported by the German Federal Ministry of Education and Research (BMBF) project Systems Biology of Metabotypes (SysMBo #0315494A). RP Allen and CJ Earley were supported by the grant PO1-AG21190 National Institute of Health, USA; the Canadian part of the study was supported by a Canadian Institutes of Health Research (CIHR) grant to GA Rouleau and J Montplaisir. D Kemlink and S Nevsimalova were supported by an ESRS grant MSM0021620849; Ja´vrova´ and K Sonka were supported by grant MSM0021620816. Recruitment of Czech controls was funded by grant IGA NR 8563-5, Ministry of Health of the Czech Republic. B Frauscher, I Cournu-Rebeix, M Francavilla, and C Fontenille are co-authors on behalf of BRC-REFGENSEP, which is supported by INSERM, AFM (Ge´ne´thon), ARSEP, and GIS-IBISA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

COMPETING INTERESTS: The authors have declared that no competing interests exist.

CITATION: Winkelmann J, Czamara D, Schormair B, Knauf F, Schulte EC, et al. (2011) Genome-Wide Association Study Identifies Novel Restless Legs Syndrome Susceptibility Loci on 2p14 and 16q12.1. PLoS Genet 7(7): e1002171. doi:10.1371/journal.pgen.1002171Winkelmann J, Czamara D, Schormair B, Knauf F, Schulte EC, et al. (2011) Genome-Wide Association Study Identifies Novel Restless Legs Syndrome Susceptibility Loci on 2p14 and 16q12.1. PLoS Genet 7(7): e1002171. doi:10.1371/journal.pgen.1002171


Prof. Juliane Winkelmann
Klinik für Neurologie und Institut für Humangenetik
Klinikum rechts der Isar
Technische Universität München (TUM)
Ismaninger Strasse 22
81675 München
Fax: ++49-89-3187-3297


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