title: Mutational and biochemical analysis of dopamine in dystonia: evidence for decreased dopamine D2 receptor inhibition.
abstract: The dystonias are a group of serious movement disorders characterized by involuntary muscle spasms of different parts of the body. We recently proposed that hypofunction of dopamine D2 receptor-mediated inhibition of the indirect output pathway of the basal ganglia can result in dystonia. In this review, we discuss the results of a variety of genetic and biochemical studies in light of this hypothesis. Several forms of early-onset dystonia show distinct autosomal dominant, recessive, or X-linked genetic transmission patterns. Late onset forms of dystonia, though not showing clear Mendelian transmission patterns, also appear to be highly familial. Recently, several genetic-linkage locations have been identified for early-onset dystonia and for two of these loci, mutations decreasing dopamine synthesis have been demonstrated. Biochemical studies of monkeys and man also demonstrate that several types of dystonia occur in a dopamine-deficiency state. Similarly, mice strains developed to be deficient in several dopamine-pathway components have motor abnormalities consistent with dystonia. Hypofunction of the dopamine D2 receptor-mediated inhibition of the indirect output pathway of the putamen may be a common feature of many of these heritable and secondary dystonic syndromes.
authors.affiliation: Department of Psychiatry, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Todd
authors.forename: J S
authors.initials: JS
authors.lastname: Perlmutter
mesh_terms: D000818:Animals; D004298:Dopamine / Q000235:genetics* / Q000502:physiology*; D004421:Dystonia / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D009154:Mutation
chemical_list: D004298:Dopamine