title: Expression of the early-onset torsion dystonia gene (DYT1) in human brain.
abstract: Early-onset torsion dystonia, an autosomal dominant disease associated with the DYT1 locus on 9q34, is the most frequent genetic form of dystonia. Recent work has revealed that the causative mutation in most cases is deletion of a glutamate residue from the carboxy terminal of torsinA, a 332 amino acid protein encoded by the DYT1 gene. To gain insight into how deletion of a single amino acid can produce such a profound movement disorder, we have mapped the expression of the DYT1 gene in normal human postmortem brain. DYT1 mRNA is highly enriched in the dopamine neurons of the substantia nigra pars compacta. Intense expression was also found in the cerebellum and hippocampal subfields. The prominent expression of the DYT1 gene within the substantia nigra pars compacta, which provides dopaminergic innervation to the basal ganglia, implicates a disturbance of dopaminergic function in the pathophysiology of early-onset torsion dystonia.
authors.affiliation: Neurology Service, Massachusetts General Hospital, and Harvard Medical School, Boston 02114, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Augood
authors.forename: J B
authors.initials: JB
authors.lastname: Penney
authors.forename: I K
authors.initials: IK
authors.lastname: Friberg
authors.forename: X O
authors.initials: XO
authors.lastname: Breakefield
authors.forename: A B
authors.initials: AB
authors.lastname: Young
authors.forename: L J
authors.initials: LJ
authors.lastname: Ozelius
authors.forename: D G
authors.initials: DG
authors.lastname: Standaert
mesh_terms: D017668:Age of Onset; D000368:Aged; D001479:Basal Ganglia / Q000737:chemistry; D001923:Brain Chemistry / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D004422:Dystonia Musculorum Deformans / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis; D013378:Substantia Nigra / Q000737:chemistry; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D018832:Molecular Chaperones; D015347:RNA Probes; D012333:RNA, Messenger; C108175:TOR1A protein, human