Grant: Operating Grant - PA: Institute of Genetics (Bridge Funding)

Our current understanding and treatment of most inherited disorders involving abnormal involuntary movements remains poor. Myoclonus dystonia (MD) is inherited as an autosomal dominant (50% of offspring are at risk of developing the disease) form of myoclonus and dystonia and is characterized by rapid muscle contractions (myoclonus) and repetitive movements resulting in abnormal postures (dystonia). Symptoms normally begin in the first or second decades of life and classically have no other associated features with the possible exception of subtle psychiatric symptoms (obsessive-compulsive disorder). MD is a genetically heterogeneous disorder with only two loci responsible for the disorder. The one known gene, e-sarcoglycan (SGCE) is on chromosome 7. Approximately 40% of IMD patients demonstrate a mutation in SGCE. The second locus, DYT15 was identified in our laboratory and is on chromosome 18. The research project is divided into three parts. Firstly, we are trying to determine the role played by SGCE in the brain. This includes identifying those proteins which interact with SGCE. Secondly, we are making a mouse model of myoclonus dystonia so that we can study the disorder and determine at a cellular level what is happening in the brain. Thirdly, we are characterizing a gene on chromosome 18 which we think also causes myoclonus dystonia. The results of this work will enable us to establish a genetic test for this disorder. It will also teach us about how this movement disorder occurs. We can then determine if pharmacological treatment will be possible.