title: Identification of a highly polymorphic microsatellite VNTR within the argininosuccinate synthetase locus: exclusion of the dystonia gene on 9q32-34 as the cause of dopa-responsive dystonia in a large kindred.
abstract: Dopa-responsive dystonia is a clinical variant of idiopathic torsion dystonia that is distinguished from other forms of dystonia by the frequent occurrence of parkinsonism, diurnal fluctuation of symptoms, and its dramatic therapeutic response to L-dopa. Linkage of a gene causing classic dystonia in a large non-Jewish kindred (DYT1) and in a group of Ashkenazi Jewish families, to the gelsolin (GSN) and arginino-succinate synthetase (ASS) loci on chromosome 9q32-34, respectively, was recently determined. Here we report the discovery of a highly informative (GT)n repeat VNTR polymorphism within the ASS locus. Analysis of a large kindred with dopa-responsive dystonia, using this new polymorphism and conventional RFLPs for the 9q32-34 region, excludes loci in this region as a cause of this form of dystonia. This provides proof of genetic heterogeneity between classic idiopathic torsion dystonia and dopa-responsive dystonia.
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Charlestown 02129.
authors.forename: D J
authors.initials: DJ
authors.lastname: Kwiatkowski
authors.forename: T G
authors.initials: TG
authors.lastname: Nygaard
authors.forename: D E
authors.initials: DE
authors.lastname: Schuback
authors.forename: S
authors.initials: S
authors.lastname: Perman
authors.forename: J M
authors.initials: JM
authors.lastname: Trugman
authors.forename: S B
authors.initials: SB
authors.lastname: Bressman
authors.forename: R E
authors.initials: RE
authors.lastname: Burke
authors.forename: M F
authors.initials: MF
authors.lastname: Brin
authors.forename: L
authors.initials: L
authors.lastname: Ozelius
authors.forename: X O
authors.initials: XO
authors.lastname: Breakefield
mesh_terms: D001124:Argininosuccinate Synthase / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9; D004276:DNA, Satellite / Q000235:genetics*; D004422:Dystonia Musculorum Deformans / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010375:Pedigree; D011110:Polymorphism, Genetic; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D004276:DNA, Satellite; D005819:Genetic Markers; D015345:Oligonucleotide Probes; D007980:Levodopa; D001124:Argininosuccinate Synthase