Developments in the molecular biology of DYT1 dystonia.
The identification of a mutation of the DYT1 gene as a cause of inherited dystonia has led to many insights regarding the genetics of this disorder. In addition, there is a rapidly expanding list of inherited dystonia syndromes, the genes for some of which have been identified or localized. The DYT1 mutation has been found in a variety of ethnic groups, and it may result in a range of phenotypes. To date, studies of torsinA, the protein product of the DYT1 gene, have not revealed its function, although its widespread distribution throughout the central nervous system suggests a universal role. TorsinA has structural homology to heat shock and chaperone proteins. Evidence from studies in cell cultures and Caenorhabditis elegans, and the presence of torsinA in inclusion bodies in several neurodegenerative diseases may be indicative of a function of this nature. Preliminary studies in humans with DYT1 dystonia and in DYT1 transgenic mice suggest disruption of the dopaminergic nigrostriatal system. A functional interference with neuronal signal processing induced by mutation of torsinA is consistent with current hypotheses regarding impairment of the center-surround mechanism in the striatum.
Walker
Ruth H
RH
Department of Neurology, Veterans Affairs Medical Center, Bronx, and Mount Sinai School of Medicine, New York, New York, USA. ruth.walker@mssm.edu
Shashidharan
P
P
D000818:Animals; D030801:Animals, Genetically Modified; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004421:Dystonia / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008967:Molecular Biology; D018832:Molecular Chaperones; D009154:Mutation
D002352:Carrier Proteins; D018832:Molecular Chaperones; C108175:TOR1A protein, human