Torsion dystonia is a movement disorder originating in the basal ganglia which affects over 200,000 individuals in North America and the USSR. Symptoms include uncontrollable muscle spasms, spastic dysphonia, contortions of the limbs, torticollis and blepharospasm. It is estimated that at least half of the cases are hereditary, with at least two genes being responsible for autosomal dominant forms of the disease and one X- linked recessive disease gene. The disease gene responsible for the most common hereditary form of the disease, which occurs in the Ashkenazic Jewish as well as other populations, has been mapped by Dr. Breakefield's and Dr. Fahn's groups to chromosome 9q34. A common genetic haplotype for the Jewish disease allele has helped to define the chromosomal region to 1 cM with highly informative flanking markers. The purpose of the USA-USSR collaborative study is to expand genetic analysis using highly polymorphic markers in this chromosomal region in order to elucidate how many different hereditary forms of this disease are caused by this disease gene, to trace the origin of the mutation in the Jewish population, and to accumulate different mutations in this disease gene which may serve to incriminate and thus identify it. This study will include clinical and genetic analysis of dystonia patients and family members in the USSR, including video recorded examinations and extensive pedigree collection. In addition, DNA will be extracted from blood samples obtained from patients and their family members and analyzed for highly polymorphic markers in this chromosomal region. Data will be analyzed through the parent NIH grant application as well as collaborative studies undertaken by Dr. Breakefield and Dr. Fahn through funding from the Dystonia Medical Research Foundation. The availability of this rich source of patient material will be invaluable in elucidating the number of different genes and mutations causing dystonia, and in identifying the disease gene on chromosome 9q34.
| Klein, C; Page, C E; LeWitt, P et al. (1999) Genetic analysis of three patients with an 18p- syndrome and dystonia. Neurology 52:649-51 |
| Klein, C; Friedman, J; Bressman, S et al. (1999) Genetic testing for early-onset torsion dystonia (DYT1): introduction of a simple screening method, experiences from testing of a large patient cohort, and ethical aspects. Genet Test 3:323-8 |
| Klein, C; Brin, M F; de Leon, D et al. (1998) De novo mutations (GAG deletion) in the DYT1 gene in two non-Jewish patients with early-onset dystonia. Hum Mol Genet 7:1133-6 |
