Our goal was to characterize patients with inherited and isolated dystonia and determine the frequency of mutations responsible for DYT1 and DYT6 in Brazilian patients.
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.
Our findings strongly suggest the role of other genetic factors or environmental triggers in the pathogenesis of dystonia related to mutations in THAP1 gene.
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).
Carriers were less likely to have dystonia restricted to a single site (11.11% in carriers vs. 65.9% in noncarriers; P < 0.01) and were less likely to have dystonia onset in cervical regions (25.9% of THAP1 carriers vs. 52.5% of noncarriers; P = 0.04).
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).
We finally discuss selected novel genes for dystonia such as KMT2B and VAC14 along with the challenges for gene identification in the NGS era and the translational importance of dystonia genetics in clinical practice.
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.
After excluding mutations in known primary dystonia genes (TOR1A, THAP1 and CIZ1), whole-exome sequencing identified a GNAL missense mutation (c.682G>T, p.V228F) in an African-American pedigree with clinical phenotypes that include cervical, laryngeal and hand-forearm dystonia.
We analyzed 610 patients with various forms of dystonia for sequence variants in the THAP1 gene by means of high resolution melting to delineate the prevalence of sequence variants and phenotypic variability.
Dystonias with known genes include DYT1 and DYT6dystonia, presenting as isolated torsion dystonia, as well as DYT5 (dopa-responsive dystonia), DYT11 (myoclonus-dystonia), and DYT12 (rapid-onset dystonia-parkinsonism), where dystonia occurs in conjunction with other types of movement disorders.
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.