title: Novel mutation in the TOR1A (DYT1) gene in atypical early onset dystonia and polymorphisms in dystonia and early onset parkinsonism.
abstract: Dystonia is a movement disorder involving sustained muscle contractions and abnormal posturing with a strong hereditary predisposition and without a distinct neuropathology. In this study the TOR1A (DYT1) gene was screened for mutations in cases of early onset dystonia and early onset parkinsonism (EOP), which frequently presents with dystonic symptoms. In a screen of 40 patients, we identified three variations, none of which occurred in EOP patients. Two infrequent intronic single base pair (bp) changes of unknown consequences were found in a dystonia patient and the mother of an EOP patient. An 18-bp deletion (Phe323_Tyr328del) in the TOR1A gene was found in a patient with early onset dystonia and myoclonic features. This deletion would remove 6 amino acids close to the carboxy terminus, including a putative phosphorylation site of torsinA. This 18-bp deletion is the first additional mutation, beyond the GAG-deletion (Glu302/303del), to be found in the TOR1A gene, and is associated with a distinct type of early onset dystonia.
authors.affiliation: Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Leung
authors.forename: C
authors.initials: C
authors.lastname: Klein
authors.forename: J
authors.initials: J
authors.lastname: Friedman
authors.forename: P
authors.initials: P
authors.lastname: Vieregge
authors.forename: H
authors.initials: H
authors.lastname: Jacobs
authors.forename: D
authors.initials: D
authors.lastname: Doheny
authors.forename: C
authors.initials: C
authors.lastname: Kamm
authors.forename: D
authors.initials: D
authors.lastname: DeLeon
authors.forename: P P
authors.initials: PP
authors.lastname: Pramstaller
authors.forename: J B
authors.initials: JB
authors.lastname: Penney
authors.forename: M
authors.initials: M
authors.lastname: Eisengart
authors.forename: J
authors.initials: J
authors.lastname: Jankovic
authors.forename: T
authors.initials: T
authors.lastname: Gasser
authors.forename: S B
authors.initials: SB
authors.lastname: Bressman
authors.forename: D P
authors.initials: DP
authors.lastname: Corey
authors.forename: P
authors.initials: P
authors.lastname: Kramer
authors.forename: M F
authors.initials: MF
authors.lastname: Brin
authors.forename: L J
authors.initials: LJ
authors.lastname: Ozelius
authors.forename: X O
authors.initials: XO
authors.lastname: Breakefield
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D017931:DNA Primers; D004422:Dystonia Musculorum Deformans / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D017384:Sequence Deletion
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D018832:Molecular Chaperones; C108175:TOR1A protein, human