Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten patients with focal dystonia of the hand, all of whom had benefited in an open-label study of botulinum toxin, were treated with botulinum toxin-A in a double-blind study. Response was assessed by three measures: (a) subjective rating, provided by patients' reports of the effect of the injections on the dystonia; (b) objective testing, consisting of manual muscle testing (MRC scale) to measure muscle strength in all patients, timing of a writing sample and counting the number of errors of writing off-the-line in six patients with writer's cramp, counting the number of errors on a standard test of transcription in two patients with stenographer's cramp, and rating by professional musicians of the performances of two patients with musician's cramp; and (c) physicians' rating, provided by a review of the patients' videotaped performance by neurologists who were unaware of which treatment was administered. Eight of the 10 patients had greater subjective improvement with botulinum toxin than with placebo, and this impression was verified by at least one objective test in six patients. Two patients failed to have a better response to botulinum toxin than to placebo, and their reports were verified by the objective tests. This study confirms the efficacy of botulinum toxin in many patients with focal hand dystonia.
 ...
PMID:Double-blind trial of botulinum toxin for treatment of focal hand dystonia. 756 28

A task-specific tremor (TST) is a rare form of movement disorder that appears while performing or attempting to perform a particular task. Primary writing tremor (PWT) is the most common form of TST which only occurs during the act of writing and hinders it. (Bain PG, Findley LJ, Britton TC, Rothwell JC, Gresty MA, Thompson PD, Marsden CD. MRC Human Movement, and Balance Unit, Institute of Neurology, London, UK. Primary writing tremor. Brain. 1995;118(6):1461-72.) Primary writing tremor type B is present not only during the act of writing but also when the hand assumes a writing posture. (Bain PG, Findley LJ, Britton TC, Rothwell JC, Gresty MA, Thompson PD, Marsden CD. MRC Human Movement and Balance Unit, Institute of Neurology, London, UK. Primary writing tremor. Brain. 1995;118(6):1461-72.) We first of all describe a remarkable case study of a 50-year old, right-handed male who started experiencing a primary writing tremor in his right hand about a year ago. This case was found to be of particular interest because the patient had it relatively difficult when attempting to write numbers as opposed to writing letters. This review further discusses the clinical manifestations of PWT. In addition, three main hypotheses have been proposed for the causation of PWT, although the exact pathophysiology of PWT still remains unknown. It has been suggested that PWT is a separate entity, a variant of essential tremor and not a separate entity, or a type of dystonia. The various treatment options for PWT are discussed including botulinum toxin and oral pharmacotherapy.
 ...
PMID:A review of primary writing tremor. 2205 Jan 92

With the possible introduction of exon skipping therapy in Duchenne muscular dystrophy, it has become increasingly important to know the role of each exon of the dystrophin gene to protein expression, and thus the phenotype. In this report, we present two related men with an unusually mild BMD associated with an exon 26 deletion. The proband, a 23-year-old man, had slightly delayed motor milestones, walking 1 1/2 years old. He had no complaints of muscle weakness, but had muscle pain. Clinical examination revealed no muscle wasting or loss of power, but his CK was 1500-7000 U/l. Muscle biopsy showed dystrophic changes. He had comorbidity with dystonia, slight mental retardation, low stature and neuropathy. The brother of the proband's mother came to medical attention when he was 43 years old. He complained about muscle pain. On examination, a MRC grade 4+ hip extention palsy and a discrete calf hypertrophy was noted. Creatine kinase was normal or raised maximally to 500 U/l. The muscle biopsy was myopathic with increased fiber size variation and many internal nuclei, but no dystrophy. No comorbidity was found. In both cases, western blot showed a reduced dystrophin band. Genetic evaluation revealed a deletion of exon 26 of the dystrophin gene in both. This is the first description of patients with a exon 26 deletion of the dystrophin gene. Assuming the proband's comorbidity is unrelated, exon 26 deletion results in a very mild phenotype. This might be of interest in planning exon skipping therapy for Duchenne muscular dystrophy. This report also shows that BMD may present with a normal CK.
 ...
PMID:Deletion of exon 26 of the dystrophin gene is associated with a mild Becker muscular dystrophy phenotype. 2261

Leigh syndrome is a subacute necrotising encephalomyopathy proven by post-mortem analysis of brain tissue showing spongiform lesions with vacuolation of the neuropil followed by demyelination, gliosis and capillary proliferation caused by mutations in one of over 75 different genes, including nuclear- and mitochondrial-encoded genes, most of which are associated with mitochondrial respiratory chain function. In this study, we report a patient with suspected Leigh syndrome presenting with seizures, ptosis, scoliosis, dystonia, symmetrical putaminal abnormalities and a lactate peak on brain MRS, but showing normal MRC enzymology in muscle and liver, thereby complicating the diagnosis. Whole exome sequencing uncovered compound heterozygous mutations in NADH dehydrogenase (ubiquinone) flavoprotein 1 gene (NDUFV1), c.1162+4A>C (NM_007103.3), resulting in skipping of exon 8, and c.640G>A, causing the amino acid substitution p.Glu214Lys, both of which have previously been reported in a patient with complex I deficiency. Patient fibroblasts showed a significant reduction in NDUFV1 protein expression, decreased complex CI and complex IV assembly and consequential reductions in the enzymatic activities of both complexes by 38% and 67%, respectively. The pathogenic effect of these variations was further confirmed by immunoblot analysis of subunits for MRC enzyme complexes in patient muscle, liver and fibroblast where we observed 90%, 60% and 95% reduction in complex CI, respectively. Together these studies highlight the importance of a comprehensive, multipronged approach to the laboratory evaluation of patients with suspected Leigh syndrome.
 ...
PMID:Whole Exome Sequencing Identifies the Genetic Basis of Late-Onset Leigh Syndrome in a Patient with MRI but Little Biochemical Evidence of a Mitochondrial Disorder. 2734 48