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.
- Juliane Winkelmann, Darina Czamara, Barbara Schormair, Franziska Knauf, Eva C. Schulte, Claudia Trenkwalder, Yves Dauvilliers, Olli Polo, Birgit Högl, Klaus Berger, Andrea Fuhs, Nadine Gross, Karin Stiasny-Kolster, Wolfgang Oertel, Cornelius G. Bachmann, Walter Paulus, Lan Xiong, Jacques Montplaisir, Guy A. Rouleau, Ingo Fietze, Jana Vávrová, David Kemlink, Karel Sonka, Sona Nevsimalova, Siong-Chi Lin, Zbigniew Wszolek, Carles Vilariño-Güell, Matthew J. Farrer, Viola Gschliesser, Birgit Frauscher, Tina Falkenstetter, Werner Poewe, Richard P. Allen, Christopher J. Earley, William G. Ondo, Wei-Dong Le, Derek Spieler, Maria Kaffe, Alexander Zimprich, Johannes Kettunen, Markus Perola, Kaisa Silander, Isabelle Cournu-Rebeix, Marcella Francavilla, Claire Fontenille, Bertrand Fontaine, Pavel Vodicka, Holger Prokisch, Peter Lichtner, Paul Peppard, Juliette Faraco, Emmanuel Mignot, Christian Gieger, Thomas Illig, H.-Erich Wichmann, Bertram Müller-Myhsok, Thomas Meitinger. Genome-Wide Association Study Identifies Novel Restless Legs Syndrome Susceptibility Loci on 2p14 and 16q12.1. PLoS Genetics, 2011; 7 (7): e1002171 DOI: 10.1371/journal.pgen.1002171
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