In the present study, we used hyperkinetic transgenic mice generated as a model of DYT1dystonia and compared the basal ganglia dopaminergic system between transgenic mice exhibiting hyperkinesia (affected), transgenic mice not showing movement abnormalities (unaffected), and non-transgenic littermates.
Our study suggests that there is an association between rs35153737 and dystonia in a southwestern Chinese population, and it may be caused by high linkage disequilibrium between this deletion and potential pathogenic variants in TOR1A.
Early onset in a limb and progression toward a generalized form, but not family history of dystonia, are indicative of DYT1dystonia in Polish dystonic individuals.
There is no evidence of neurodegeneration in DYT1dystonia, which suggests that mutant TA leads to functional neuronal abnormalities, leading to dystonic movements.
We used a multidisciplinary approach to investigate the responses to mu activation in 2 mouse models of DYT1dystonia (Tor1a<sup>+/Δgag</sup> mice, Tor1a<sup>+/-</sup> torsinA null mice, and their respective wild-types).
The authors report on 2 cases of pediatric generalized dystonia with a DYT1 mutation; the patients, an 11-year-old girl and a 9-year-old boy, underwent chronic, pallidal deep brain stimulation (DBS) of the globus pallidus internus (GPi).
Analysis of 83 published series including 5,057 patients indicated significant differences in the mean age at onset of five phenotypes of PTD (mean age at onset; 95% CI): DYT1dystonia (11.3 years; 10.3 to 12.2), writer's cramp (38.4; 36.9 to 39.9), CD (40.8; 40.3 to 41.3), spasmodic dysphonia (43.0; 42.2 to 43.9), and blepharospasm-oromandibular dystonia (55.7; 55.1 to 56.4).
Moreover, dystonia and Parkinson disease share the common feature of reduced dopamine neurotransmission in the striatum, so we assumed that mutations in the DYT1 gene might have the same role in cases of early onset primary torsion dystonia (EOPTD) and early onset Parkinson disease (EOPD) that present dystonia.
We screened the entire coding sequence and the 5'-UTR region of TOR1A for rare non-ΔGAG sequence variants in a large series of 940 individuals with various forms of isolated dystonia as well as in 376 ancestry-matched controls.
In contrast, ʟ-DOPA, which is not usually effective for the treatment of DYT1dystonia, did not increase dopamine release in either Dyt1 or control mice.
Mutational analysis of most of the coding region and splice junctions of TOR1A and TOR1B did not reveal additional mutations in typical early onset cases lacking the GAG deletion (N = 17), in dystonic individuals with apparent homozygosity in the 9q34 chromosomal region (N = 5), or in a representative Ashkenazic Jewish individual with late onset dystonia, who shared a common haplotype in the 9q34 region with other late onset individuals in this ethnic group.
The authors screened 197 patients with dystonia (generalized: n = 5; focal/segmental: n = 126; myoclonus-dystonia: n = 34; neuroleptic-induced: n = 32), 435 with PD, and 42 with various other movement disorders, along with 812 healthy controls, for small deletions in exon 5 of DYT1 and tested for exon rearrangements by quantitative, duplex PCR in 51 GAG deletion-negative dystonia cases.
Genetic testing excluded the rapid-onset dystonia-parkinsonism locus (DYT12; OMIM*128235), autosomal recessive Parkin locus (PARK2; OMIM *602544), and DYT1dystonia.