What is dystonia?
Dystonia is a state of abnormal (either excessive or inadequate) muscle tone. There are many forms of dystonia. Dystonia disorders cause involuntary movements and prolonged muscle contraction, resulting in twisting body motions, tremor, and abnormal posture. These movements may involve the entire body, or only an isolated area.
There are several situations that are associated with dystonia, including medication-induced and dystonia resulting from a specific form of lung cancer. Symptoms may even be "task specific," such as writer's cramp.
A form of dystonia known as early-onset torsion dystonia (also called idiopathic or generalized torsion dystonia) begins in childhood around the age of 12. Symptoms typically start in one part of the body, usually in an arm or leg, and eventually spread to the rest of the body within about 5 years. Early-onset torsion dystonia is not fatal, but it can be severely debilitating. Most children with the disorder are unable to perform the simplest of motor tasks and are confined to a wheelchair by the time they reach adulthood.
What is the cause of dystonia?
Researchers believe that dystonia may be caused by a breakdown of the dopamine system in the basal ganglia, a collection of structures in the brain that control movement. Dopamine is a neurotransmitter that regulates communication between the nerves within the basal ganglia. A malfunctioning dopamine system in the basal ganglia is responsible for many movement disorders, including Parkinson's disease. Researchers have mapped a total of seven genes causing dystonia and sequenced two that code for proteins involved in dopamine systems. Dopamine therapy seems to work for some kinds of dystonia, but is not effective for children with generalized torsion dystonia.
Scientists have identified the gene responsible for early-onset torsion dystonia and have found a new class of proteins that may provide insight into all of the dystonia disorders. The discovery of the gene will make diagnosis of early-onset torsion dystonia easier and allow scientists to investigate other factors that might contribute to the disease. The study, supported by the National Institute of Neurological Disorders and Stroke (NINDS), was published in the September 1997 issue of Nature Genetics. "The cloning of this gene is a long sought-after goal," says Zach W. Hall, Ph.D., Director of the NINDS. "Its discovery is a signal achievement which will help us understand the pathological basis of dystonia and other movement disorders."
NINDS grantees, Xandra O. Breakefield, Ph.D., and Laurie J. Ozelius, Ph.D., neurogeneticists at Massachusetts General Hospital (MGH) in Boston and lead authors of the study, have been searching for the dystonia gene for more than 15 years. Their team included investigators at Columbia Presbyterian Medical Center and Mt. Sinai Hospital in New York City, Stanford University in Stanford, California, and Oregon Health Sciences University in Portland, Oregon. In 1989 the team localized or mapped the gene to chromosome 9 and named it DYT1. Now, they have sequenced the DYT1 gene and found that it codes for a previously unknown protein which the team named "torsinA."
"TorsinA is a protein we've never seen before," says Dr. Breakefield, "but we already have clues about its function because it resembles a class of proteins that protects cells from stress and trauma." Once they sequenced the DYT1 gene, the investigators compared it to other genes from a large database of genetic information. The DYT1 gene resembled genes that code for proteins responsible for binding adenosine triphosphate (ATP), the energy-containing molecules of cells. TorsinA and related ATP-binding proteins resemble a class of proteins called heat-shock proteins.
Heat-shock proteins act as thermoregulators to other proteins involved in cellular function and metabolism. They protect proteins from temperature fluctuations and help proteins maintain their shape. By maintaining the strength and resiliency of cellular proteins, heat-shock proteins protect cells from deadly environmental, biological, and chemical stress.
|
