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.
The DYT1 mutation was also detected in 2 patients with multifocal dystonia, 1 of them presenting with involvement of cranial and cervical muscles, and in 2 patients with writer's cramp of both hands with only slight progression.
Twelve dystonia patients manifesting the disease, seven nonmanifesting dystonia mutation carriers (DYT1 and DYT6 gene mutations), and eight age-matched normal control subjects were imaged for a previous study.
Evidence suggests that TOR1A mutation produces dystonia through an aberrant neuronal signalling within the striatum, where D2 dopamine receptors (D2R) produce an abnormal excitatory response in cholinergic interneurons (ChIs) in different models of DYT1 dystonia.
The authors report a Chinese boy with a DYT1 gene mutation having muscle stiffness, severe painful muscle spasm, myoclonus, and dystonia compatible with stiff child syndrome.
We identified a de novo delGAG mutation in the TOR1A gene in a patient with a typical DYT1 phenotype and a novel c.1A > G (p.Met1?) mutation in THAP1 in a patient with early onset generalized dystonia with speech involvement.
Although clinically similar to most cohorts with dystonia worldwide, the classical mutation (c.907_909delGAG) in TOR1A (causing DYT1) is absent in our patients.
We have used a transgenic mouse model of DYT1dystonia [human mutant-type (hMT)1 mice] to examine the effect of the mutant human torsinA protein on striatal dopaminergic function.
TOR1A (torsinA, DYT1) is the leading cause of early-onset generalized dystonia, however, the associations between common TOR1A single nucleotide polymorphisms (SNPs) and primary adult-onset focal dystonia are controversial.
Although mutations in DYT1 are associated with a rare form of heritable generalized dystonia, the native function of torsinA seems to be cytoprotective in maintaining the cellular threshold to endoplasmic reticulum (ER) stress.
These results suggest that an imbalanced striatal dopaminergic/cholinergic signaling occurs early in DYT1dystonia and persists along development, representing a susceptibility factor for symptom generation.
To analyze contribution of rs3842225 and rs1182 single nucleotide polymorphisms (SNP) in TOR1A gene, the causative gene for the DYT1 form of hereditary early-onset generalized dystonia, to the development of focal and segmental dystonia in Russian patients.