DYT6 dystonia: mutation screening, phenotype, and response to deep brain stimulation.
Summary of "DYT6 dystonia: mutation screening, phenotype, and response to deep brain stimulation."
Mutations in THAP1, a gene encoding a nuclear pro-apoptotic protein, have been associated with DYT6 dystonia. First reports on the phenotype of DYT6 dystonia show an early onset dystonia with predominant cranio-cervical and laryngeal involvement. Here we assessed the frequency and phenotype of THAP1 mutation carriers in a large Dutch cohort of adult-onset (≥26 years) dystonia (n = 388) and early-onset dystonia (n = 67) patients. We describe the phenotype of DYT6 dystonia patients and their response on GPi DBS. Overall, 3 nonsynonymous heterozygous mutations were detected in the early-onset group (4.5%). Two DYT6 families were identified, showing a heterozygous phenotype. All patients had segmental or generalized dystonia, often associated with profound oromandibular and laryngeal involvement. No nonsynonymous mutations were found in patients with adult-onset focal dystonia. Rare synonymous variants were identified in conserved regions of THAP1, two in the adult-onset cervical dystonia group and one in the control group. Four DYT6 dystonia patients were treated with GPi DBS with moderate to good response on motor function but marginal benefit on speech.
Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
This article was published in the following journal.
Name: Movement disorders : official journal of the Movement Disorder Society
Several genes associated with dystonia have been identified. A mutation in one of these, THAP1 (DYT6), is linked to isolated dystonia. The aim of this study was to assess the prevalence of THAP1 gene ...
We describe the case of a 42-year-old Japanese woman with childhood-onset myoclonus, dystonia, and psychiatric symptoms, including anxiety, phobia, and exaggerated startle response. The diagnosis was ...
Generalized dystonia, both primary and secondary forms, and axial dystonias such as tardive dystonia, and idiopathic cervical dystonia are responsive to globus pallidus interna (GPi) DBS. There is a p...
To investigate the effect of deep brain stimulation (DBS) on reducing dystonia and disability in adults with cerebral palsy (CP) and to compare the therapeutic outcomes between primary dystonia patien...
Pallidal deep brain stimulation (GPi-DBS) effectively ameliorates idiopathic dystonia, although approximately 15% of patients respond insufficiently. Although various thalamic and subthalamic targets ...
RATIONALE: Dystonia is a disorder in which the muscles that control voluntary movements are persistently or intermittently contracted (not relaxed). Deep brain stimulation is provided by a...
The purpose of this study is to allow patients to undergo deep brain stimulation (DBS) surgery for the treatment of dystonia. This is NOT a research study, but rather, a requirement by th...
The purpose of this study is to evaluate the safety and effectiveness of deep brain stimulation (DBS) of the subthalamic nucleus (STN)for dystonia.
The purpose of this randomized, double blind, multi-center study is to assess the efficacy and safety of bilateral pallidal deep brain stimulation in patients with tardive dystonia.
Primary generalized dystonia, also called idiopathic torsion dystonia or dystonia musculorum deformans is a disabling neurological condition which usually starts in childhood, mostly in a ...
Medical and Biotech [MESH] Definitions
Mutation process that restores the wild-type PHENOTYPE in an organism possessing a mutationally altered GENOTYPE. The second "suppressor" mutation may be on a different gene, on the same gene but located at a distance from the site of the primary mutation, or in extrachromosomal genes (EXTRACHROMOSOMAL INHERITANCE).
Genes that have a suppressor allele or suppressor mutation (SUPPRESSION, GENETIC) which cancels the effect of a previous mutation, enabling the wild-type phenotype to be maintained or partially restored. For example, amber suppressors cancel the effect of an AMBER NONSENSE MUTATION.
The identification of selected parameters in newborn infants by various tests, examinations, or other procedures. Screening may be performed by clinical or laboratory measures. A screening test is designed to sort out healthy neonates (INFANT, NEWBORN) from those not well, but the screening test is not intended as a diagnostic device, rather instead as epidemiologic.
This type of gonadal defect is characterized by a female phenotype, normal to tall stature, bilateral streak or dysgenetic gonads, and a 46,XY karyotype. This XY gonadal dysgenesis is a heterogenous condition with variant forms resulting from a structural abnormality on Y chromosome, a mutation in SRY gene or a mutation in autosomal genes. The syndrome is sometimes called "pure gonadal dysgenesis," but this designation may also refer to gonadal dysgenesis with a 46,XX karyotype (GONADAL DYSGENESIS, 46,XX).
The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.