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.
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.
Kwiatkowski
D J
DJ
Department of Medicine, Massachusetts General Hospital, Charlestown 02129.
Nygaard
T G
TG
Schuback
D E
DE
Perman
S
S
Trugman
J M
JM
Bressman
S B
SB
Burke
R E
RE
Brin
M F
MF
Ozelius
L
L
Breakefield
X O
XO
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
D004276:DNA, Satellite; D005819:Genetic Markers; D015345:Oligonucleotide Probes; D007980:Levodopa; D001124:Argininosuccinate Synthase