geneIn 1997, researchers identified the DYT1 gene responsible for early-onset generalized dystonia. The DYT1 gene codes for a previously unknown protein, named "torsinA," and it has significant similarities to the heat-shock proteins and chaperone proteins. Found in virtually all living organisms, the heat-shock proteins help cells recover from stresses including heat, traumatic injury, and chemical poisoning. Until now, no human disease has ever been associated with these proteins
In people with early-onset dystonia, the DYT1 gene has a mutation that causes the deletion of three "letters" or bases—specifically a “GAG” deletion—in the genetic code. This GAG deletion results in the loss of an amino acid, called glutamic acid, which is a component of the torsinA protein. This relatively small change in the torsinA blueprint apparently causes critical changes in the function of the protein. The role of the torsinA protein is currently unknown, but somehow this defective protein disrupts communication among the neurons responsible for movement and muscle control, leading to the symptoms of the dystonia disorder
Researchers believe that the same mutation in the DYT1 gene appeared independently in several ethnic populations throughout history and is possibly one of only a few mutations that result in early-onset dystonia. Exactly how the abnormal gene causes the dystonia is presently unknown
Inheritance of DYT1
DYT1 generalized dystonia is inherited in an autosomal dominant manner, meaning that only one parent needs to have a copy of the mutated DYT1 gene for a child to inherit the disorder. If one parent has the mutated gene, there is a 50% chance that a child will inherit that gene. However, simply having the mutated gene does not necessarily mean that a person will develop the disorder. This phenomenon is called variable penetrance. For reasons that scientists do not yet understand, only 30 to 40% of those with the abnormal DYT1 gene ever develop symptoms of dystonia—that means that 60 to 70% of people who carry this gene never manifest symptoms. If a person has the DYT1 mutation (with or without symptoms), there is about a 15% chance that his/her children will develop dystonia. There is no way yet to predict whether a person with the abnormal gene will develop symptoms of the disorder, and the severity of the illness may differ markedly within a family
DYT1 Testing
Genetic testing is now available for individuals affected with early-onset or limb-onset dystonia. This test specifically identifies the specific mutation in the DYT1 gene that is associated with dystonia. Using DNA obtained from a small blood sample, this test analyzes for the presence of the known GAG deletion. It allows for diagnostic testing, confirmation of the diagnosis, carrier status, prenatal testing, and preimplantation genetic diagnosis. Testing is usually reserved for people who develop dystonia as children without the symptoms of other neurological disorders, or develop dystonia in the limbs. This test is unlikely to be positive for individuals with late-onset, primarily cervical or cranial dystonia, or blepharospasm, unless there is a family history of early-onset dystonia
The testing for the DYT1 gene is performed through a local neurologist, and all persons who are considering a genetic test for the DYT1 mutation should consult a genetic counselor
