DMRF-funded Scientists Discover New Genetic Basis for Dystonia
Discovery of New Gene Provides Opportunity to Better Understand Focal and Generalized Dystonias

Scientists from Mount Sinai School of Medicine and Beth Israel Medical Center have announced the latest discovery in dystonia research: a novel gene for primary torsion dystonia, which includes adult onset focal dystonia and early onset dystonia. The Dystonia Medical Research Foundation (DMRF) is proud to have partially supported this work.

This discovery was made through the collaboration of the molectular genetic laboratory of Dr. Laurie Ozelius at Mount Sinai and the clinical research team led by Dr. Susan Bressman at Beth Israel, as well as movement disorder specialists in the US and Canada. Ultimately, this work derived from the generosity of patients and families who participated in these studies for over a 25 year period. Many responded through advertisements placed in the DMRF's Dystonia Dialogue newsletter to participate in the NIH-Funded parent study.

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

“The technique used for the identification of the GNAL gene—called exome sequencing—is 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 research team. “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 Mount Sinai School of Medicine, who is first author of the paper.

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. Primary torsion dystonia may be adult onset or childhood onset. Symptoms can be focal, segmental or generalized. The disorder is dominantly inherited with reduced penetrance, making it difficult to predict which family members may at risk without genetic screening. Three additional genes associated with primary torsion dystonia have been identified: DYT1, THAP1, and CIZI.

Art Kessler, President of the DMRF says, “We’re delighted that we were able to support this research into the underlying genetic basis of dystonia. It’s especially exciting that this gene appears relevant to families impacted by focal and generalized dystonias—adult onset and childhood onset forms of the disorder. This research has the potential to lead to new diagnostic tools and novel treatments for many of us in the dystonia community.”

Susan Bressman, MD, Chair of Neurology at Beth Israel Medical Center also noted “this study emphasizes the great utility of a truly long term collaborative study of patients and families, including families spread out throughout North America. And the importance of investing in the clinical and laboratory infrastructure so we keep the study of these patients and families an ongoing venture.” 

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 Santé et la Recherche Médicale (INSERM). The abstract may be found at: http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.2496.html

Click here or go to www.dystonia-foundation.org/research to learn more about the DMRF’s research efforts.

12/18/12

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