NEW YORK, Dec. 26, 2012 /PRNewswire/ --Scientists from Beth Israel Medical Center and the Icahn School of Medicine at Mount Sinai have announced the discovery of a novel gene for primary torsion dystonia, a debilitating neurological disorder estimated to affect no fewer than 300,000 people in the US and Canada.

Published online December 9 in Nature Genetics, the findings describe the GNAL gene, the first primary torsion dystonia gene that directly points to pathways in the brain's dopamine system as the origin of pathophysiology. Genetic study in two extensively studied dystonia families revealed mutations in GNAL. Further screening of 39 additional affected families identified another six mutations in this gene. The research unveils a new potential therapeutic target and thus an opportunity for developing new treatments. This discovery will also help development of genetic tests to confirm diagnosis, identify unaffected adult carriers, and provide greater reproductive health options for affected families.

The discovery was made through the collaboration of a clinical research team of movement disorder specialists in the United States and Canada led by Susan Bressman, MD, Chair of the Mirken Department of Neurology at Beth Israel Medical Center and the work of the molecular genetic laboratory at the Icahn School of Medicine at Mount Sinai, led by Laurie Ozelius, PhD, Associate Professor in the Department of Genetics and Genomic Sciences there. "Ultimately, this work derived from the generosity of patients and families who participated in these studies for a 25 year period," says Dr. Bressman. "The study emphasizes the great utility of a truly long-term, collaborative study of patients and families and the importance of investing in the clinical and laboratory infrastructure to keep the study of these patients and families an ongoing venture."

Primary torsion dystonia is a movement disorder characterized by repetitive twisting muscle contractions and postures that can affect the face, neck, arms, legs, or torso. Common symptoms include tremors, voice problems, or a dragging foot. Adults and children of all backgrounds may be affected. The disorder is dominantly inherited with reduced penetrance, making it difficult to predict which family members may be at risk without genetic screening. Three additional genes associated with primary torsion dystonia have been identified.

"The technique used for the identification of the GNAL genecalled exome sequencingis a powerful and efficient tool that will accelerate the pace of dystonia gene discovery and, consequently, our understanding of the pathways involved in primary torsion dystonia," says Dr. Ozelius, who led the laboratory effort.

"Any new gene offers the potential to develop new therapeutics, but because GNAL belongs to a well studied pathway, other components in this pathway may also be targets for drug development" adds Tania Fuchs, PhD, Instructor in the Department of Genetics and Genomic Sciences of the Icahn School of Medicine at Mount Sinai, who is first author of the paper.

This research was funded in part by the Dystonia Medical Research Foundation, the Bachmann-Strauss Dystonia & Parkinson's Foundation, and the National Institute of Health (NIH).

Study authors also include scientists from Scripps Research Institute; Toronto Western Hospital, University of California, San Francisco; Emory University School of Medicine;, Jefferson Hospital for Neuroscience, Massachusetts General Hospital and Institute National de la Sante et la Recherche Medicale (INSERM).

The abstract may be found at: http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.2496.html

About the Dystonia Medical Research Foundation:Founded in 1976, the Dystonia Medical Research Foundation (DMRF) is a 501(c)3 non-profit organization dedicated to serving people with dystonia and their families. The DMRF has grown from a small family-based foundation into a dynamic membership-driven organization led by a Board of Directors and network of volunteers with personal connections to dystonia. For over 36 years, the DMRF has supported and stimulated the field of dystonia research. Work supported by the DMRF has led to an overall better understanding of dystonia as well as breakthroughs in genetics and therapeutics. In addition to funding investigators, the scientific program of the DMRF includes contracts with pharma/biotech companies on targeted projects, scientific meetings and workshops, a clinical fellowship program, brain bank collective, international medical symposiums, and serving as an administrative center for the Dystonia Coalition. The Medical and Scientific Advisory Council (MSAC) is comprised of pre-eminent researchers and clinicians from various scientific disciplines. The members are responsible not only for grant review but also for setting the direction of the research to find more effective treatments and ultimately a cure.

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