Here, I review the clinical genetics and cell biology of three forms of inherited dystonia for which the causative mutation is known: DYT1 (TOR1A), DYT6 (THAP1), DYT25 (GNAL).
To date gene loci have been identified in at least six autosomal dominant forms, i.e., in idiopathic torsion dystonia (9q34), focal dystonia (18p), adult-onset idiopathic torsion dystonia of mixed type (8p21-q22), dopa-responsive dystonia (14q22.1-q22.2), and paroxysmal dystonic choreoathetosis (2q25-q33; 1p21-p13.3).
Neurophysiological studies on DYT1 and DYT6 patients, as well as on nonmanifesting carriers, have demonstrated the presence of altered synaptic plasticity.
Microelectrode recordings made during the DBS procedures demonstrated no differences in the firing patterns of GPi neurons from DYT1 and DYT6 patients.
Intraoperative microelectrode recordings under general anesthesia in two of the patients showed no difference between THAP1 and previously operated DYT1 MutC.
We recruited 8 DYT1 gene carriers with dystonia, 6 DYT1 gene carriers without dystonia, 6 patients with sporadic primary dystonia (torticollis), and 10 healthy control subjects.Groups were age-matched.
Mutations in the thanatos-associated protein domain containing apoptosis-associated protein 1 gene (THAP1) are responsible for adult-onset isolated dystonia (DYT6).
Like other genetic primary dystonias, DYT6 patients have no characteristic neuropathology, and mechanisms by which mutations in THAP1 cause dystonia are unknown.
Here, I review the clinical genetics and cell biology of three forms of inherited dystonia for which the causative mutation is known: DYT1 (TOR1A), DYT6 (THAP1), DYT25 (GNAL).
Here we report a novel mutation in the THAP1 gene identified in a Polish family with DYT6 phenotype - the c.15C>G substitution in exon 1 introducing the missense mutation p.Cys5Trp within the N-terminal THAP domain.