DYT1 dystonia is an inherited movement disorder caused by mutations in DYT1 (TOR1A), which codes for torsinA. Most of the patients have a trinucleotide deletion (ΔGAG) corresponding to a glutamic acid in the C-terminal region (torsinA(ΔE)). Dyt1 ΔGAG heterozygous knock-in (KI) mice, which mimic ΔGAG mutation in the endogenous gene, exhibit motor deficits and deceased frequency of spontaneous ex...

Primary dystonia is a disease characterized by involuntary twisting movements caused by CNS dysfunction without underlying histopathology. DYT1 dystonia is a form of primary dystonia caused by an in-frame GAG deletion (DeltaE302/3) in the TOR1A gene that encodes the endoplasmic reticulum luminal protein torsinA. We show that torsinA is also present in the nuclear envelope (NE), where it appears...

A GAG deletion in the DYT1 gene accounts for most early, limb onset primary torsion dystonia (PTD). The genetic bases for the more common adult onset and focal PTD are less well delineated. Genetic loci for an "intermediate dystonia" phenotype and for torticollis, named DYT6 and DYT7 respectively, have recently been mapped in single families. To evaluate the contribution of these genetic loci t...

BACKGROUND Spatial discrimination thresholds (SDTs) assess somatosensory integration, and provide a window into better understanding the pathophysiology of dystonia. They are abnormal in some focal dystonias, but normal in DYT1 dystonia. It is unknown whether SDTs are altered in DYT6 gene mutation carriers (C). METHODS SDTs were assessed in 17 DYT6 C (including eight manifesting carriers), 15...

DYT1 dystonia, the most common inherited form of primary dystonia, is a neurodevelopmental disease caused by a dominant mutation in TOR1A. This mutation ('ΔE') removes a single glutamic acid from the encoded protein, torsinA. The effects of this mutation, at the molecular and circuit levels, and the reasons for its neurodevelopmental onset, remain incompletely understood. To uniquely address ke...

EDITOR—Torsion dystonia is a movement disorder characterised by sustained involuntary muscle contractions, frequently causing twisting and repetitive movements or abnormal postures. Primary torsion dystonia (PTD) occurs either in a familial or sporadic pattern with dystonia as the sole phenotypic manifestation with the exception that tremor can be present as well. Early onset, generalised torsi...

BACKGROUND DYT1 early-onset generalized dystonia is a neurological movement disorder characterized by involuntary muscle contractions. It is caused by a trinucleotide deletion of a GAG (ΔGAG) in the DYT1 (TOR1A) gene encoding torsinA; the mouse homolog of this gene is Dyt1 (Tor1a). Although structural and functional alterations in the cerebellum have been reported in DYT1 dystonia, neuronal mor...

Rapid onset dystonia-parkinsonism (RDP) is a rare movement disorder with autosomal dominant inheritance, characterised by sudden onset of dystonic spasms and slowness of movement. To date, three families have been described that share linkage to the same location on chromosome 19q13, designated DYT12. Very recently, mutations in the ATP1A3 gene at the DYT12 locus have been demonstrated in seven...

Early-onset primary dystonia is an inherited disorder characterized by involuntary twisting, repetitive movements and abnormal postures. It has recently been demonstrated that the DYT1 gene is the most relevant gene associated with primary generalized dystonia. The DYT1 gene product is a 332-aminoacid long protein, termed TorsinA, whose function is still not clear. Based on the results obtained...