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)

A family with a syndrome of mental retardation, dystonic movements of the hands, and dysarthria (MIM no. 309510) was described and mapped to Xp22 by Partington et al. (Am J Med Genet 1988; 30:251-262). The original localization encompassed the distal half of the short arm of the X chromosome, with a peak lod score of 2.1 at the DXS41 locus. The gene localization for this disorder (PRTS) has now been refined using recently characterized dinucleotide repeat markers. The PRTS gene maps between DXS365 and DXS28, an interval estimated to be less than 15 cM. A peak lod score of 3.01 at a recombination fraction of zero was generated by 2-point linkage analysis with the marker DXS989. Dystonic movements may be progressive and could be overlooked in children. Clinical assessments of affected men who are mentally retarded should be critically evaluated for this manifestation, where they belong to families in which the gene localization overlaps with PRTS.
 ...
PMID:X-linked mental retardation with dystonic movements of the hands (PRTS): revisited. 794 40

The Mohr-Tranebjaerg syndrome (MIM 304700) and the Jensen syndrome (MIM 311150) were previously reported as separate X-linked recessive deafness syndromes associated with progressive visual deterioration, dystonia, dementia, and psychiatric abnormalities. In the most extensively studied Norwegian family, the Mohr-Tranebjaerg syndrome was reported to be caused by a one-basepair deletion (151delT) in the deafness/dystonia peptide (DDP) gene at Xq22. This gene has been renamed TIMM8a. We identified a stop mutation (E24X) in the TIMM8a gene segregating with the disease in the original Danish family with the Jensen syndrome, which confirms that the two disorders are allelic conditions. We also report abnormal VEP examinations and neuropathological abnormalities in affected males from the two unrelated families with different mutations. The findings included neuronal cell loss in the optic nerve, retina, striate cortex, basal ganglia, and dorsal roots of the spinal cord. The demonstration of mitochondrial abnormalities in skeletal muscle biopsies in some patients is compatible with the suggestion from recent research that the TIMM8a protein is the human counterpart of an intermembrane mitochondrial transport protein, Tim8p, recently characterized in yeast. The clinical and neuropathological abnormalities associated with mutations in the TIMM8a gene support that this X-linked deafness-dystonia-optic neuropathy syndrome is an example of progressive neurodegeneration due to mutations in a nuclear gene necessary for some, yet unknown mitochondrial transport function. We recommend sequencing the TIMM8a gene, thorough ophthalmological examination, and measuring visual evoked potentials in clinically suspected male patients with either progressive hearing impairment, dystonia, or visual disability in order to establish an early diagnosis and provide appropriate genetic counselling.
 ...
PMID:Neuronal cell death in the visual cortex is a prominent feature of the X-linked recessive mitochondrial deafness-dystonia syndrome caused by mutations in the TIMM8a gene. 1180 87

Benign hereditary chorea (BHC) (MIM 118700) is an autosomal dominant movement disorder. The early onset of symptoms (usually before the age of 5 years) and the observation that in some BHC families the symptoms tend to decrease in adulthood suggests that the disorder results from a developmental disturbance of the brain. In contrast to Huntington disease (MIM 143100), BHC is non-progressive and patients have normal or slightly below normal intelligence. There is considerable inter- and intrafamilial variability, including dysarthria, axial dystonia and gait disturbances. Previously, we identified a locus for BHC on chromosome 14 and subsequently identified additional independent families linked to the same locus. Recombination analysis of all chromosome 14-linked families resulted initially in a reduction of the critical interval for the BHC gene to 8.4 cM between markers D14S49 and D14S278. More detailed analysis of the critical region in a small BHC family revealed a de novo deletion of 1.2 Mb harboring the TITF-1 gene, a homeodomain-containing transcription factor essential for the organogenesis of the lung, thyroid and the basal ganglia. Here we report evidence that mutations in TITF-1 are associated with BHC.
 ...
PMID:Mutations in TITF-1 are associated with benign hereditary chorea. 1197 78

Partington et al. [1988] described a three-generation family (MRXS1, MIM *309510, PRTS) with a syndromic form of X-linked mental retardation (XLMR). The clinical features in 10 affected males included mild to moderate MR, dystonic movements of the hands, and dysarthria. After refinement, the PRTS locus was mapped to marker DXS989 (with maximum LOD score of 3.1) with flanking markers DXS365 and DXS28. Since then, no other patients with a similar phenotype have been described. We present a detailed description of the neurological symptoms and the disease history of two brothers with the clinical features of PRTS. Psychomotor development was delayed in both, and neurological features included mild to moderate mental retardation, dysarthria, facial muscle weakness, severe dysdiadochokinesis, slow dystonic movements, and mild spasticity of the hands, without ataxia or spasticity of the legs. The symptoms were nonprogressive and extrapyramidal, and without cerebellar involvement. In general, behavior of the two brothers was friendly and quiet, although the elder brother had periods of depressed mood and outbursts of anger. Karyotypes and subsequent investigation of the subtelomeres as well as DNA analysis of the FMR1 gene, the androgen receptor gene, and the DM locus did not reveal a genetic abnormality. Haplotype analysis showed that the affected brothers share the PRTS region at Xp22.1. Mutation screening of the PDH-E1alpha gene did not reveal a pathogenic mutation.
 ...
PMID:Clinical study and haplotype analysis in two brothers with Partington syndrome. 1237 38

Two families, originally diagnosed as having nonsyndromic X-linked mental retardation (NSXLMR), were reviewed when it was shown that they had a 24-bp duplication (428-45 1dup(24bp)) in the ARX gene [Stromme et al., 2002: Nat Genet 30:441-445]. This same duplication had also been found in three other families: one with X-linked infantile spasms and hypsarrhythmia (X-linked West syndrome, MIM 308350) and two with XLMR and dystonic movements of the hands (Partington syndrome, MIM 309510). On review, manifestations of both West and Partington syndromes were found in some individuals from both families. In addition, it was found that one individual had autism and two had autistic behavior, one of whom had epilepsy. The degree of mental retardation ranged from mild to severe. A GCG trinucleotide expansion (GCG)10+7 and a deletion of 1,517 bp in the ARX gene have also been found in association with the West syndrome, and a missense mutation (1058C>T) in a family with a newly recognized form of myoclonic epilepsy, severe mental retardation, and spastic paraplegia [Scheffer et al., 2002: Neurology, in press]. Evidently all these disorders are expressions of mutations in the same gene. It remains to be seen what proportions of patients with infantile spasms, focal dystonia, autism, epilepsy, and nonsyndromic mental retardation are accounted for by mutations in the ARX gene.
 ...
PMID:Variable expression of mental retardation, autism, seizures, and dystonic hand movements in two families with an identical ARX gene mutation. 1237 46

Pantothenate kinase-associated neurodegeneration (PKAN) (MIM 234200; Hallervorden-Spatz syndrome) is a degenerative, autosomal recessive disorder in childhood, currently without specific treatment. In contrast to variable clinical features, T2-weighted magnetic resonance images show a characteristic 'eye-of-the-tiger sign' in the globus pallidus due to excess iron deposition. Recently a defect in pantothenate kinase, the key regulatory enzyme in the synthesis of coenzyme A from pantothenate, has been identified as the cause of the disease. We report a 12-year-old boy with progressive rigidity, dystonia, impaired voluntary movement, dysarthria, and mental deterioration. Over 10 years the boy had been misdiagnosed with clumsiness, emotional and behavioural deficits, and attention deficit disorder, before neuroimaging was performed showing the characteristic 'eye-of-the-tiger sign'. Molecular analyses confirmed two mutations in the PANK2 gene [coding sequence of a gene that has homology to murine pantothenate kinase-1]. We conclude that in progressive childhood dystonia, PKAN should be considered and magnetic resonance imaging performed early. The newly described defect of the pantothenate kinase enzyme enables a novel therapeutic approach to be considered, based on the mutation analyses of the PANK2 gene, as well as the prenatal diagnosis of this disorder.
 ...
PMID:Progressive dystonia in a 12-year-old boy. 1269 33

Rapid-onset dystonia-parkinsonism (RDP, DYT12, MIM 128235) is a rare autosomal dominant movement disorder characterized by abrupt onset of slow, dystonic movements and prominent bulbar features. Three families and 1 isolated case have been described in the literature, and linkage to markers on chromosome 19q13 have been reported. Here, we describe the clinical features in a fourth family (the second in Europe) with 4 affected members, suggesting that RDP may be misdiagnosed for years and/or may mimic other dystonic/parkinsonian syndromes. By using haplotype analysis, we show that the family is consistent with linkage to markers on chromosome 19q13.
 ...
PMID:Rapid-onset dystonia-parkinsonism: a fourth family consistent with linkage to chromosome 19q13. 1539 49

Neuroferritinopathy (MIM 606159, also labeled hereditary ferritinopathy and neurodegeneration with brain iron accumulation type 2, NBIA2) is an adult-onset progressive movement disorder caused by mutations in the ferritin light chain gene (FTL1). Four pathogenic mutations in FTL1 have been described to date; 460insA was our original founder mutation in Cumbria, North West England, where it arose before 1800. The same mutation appears to have arisen separately in France. The resulting altered reading frame extends the peptide, disrupting the ferritin dodecahedron structure and causing accumulation of ferritin and iron, primarily in central neurons. A wide range of neurologic symptoms may occur; 50% present with chorea, 43% with limb dystonia, and 7% with Parkinsonian features. The disorder provides a direct link between disordered iron storage and a neurodegenerative disease, opening new avenues for treatment by altering brain iron stores in addition to symptomatic treatments such as local Botulinum toxin and oral anti oxidants.
 ...
PMID:Neuroferritinopathy. 1710 56

The deafness-dystonia syndrome (DDS) or Mohr-Tranebjaerg syndrome (MTS, MIM 304700) is a rare X-linked recessive neurological disorder resulting from loss-of-function mutations in the nuclear DDP1/TIMM8A gene, involved in the transport and sorting of proteins to the mitochondrial inner membrane. A Mohr-Tranebjaerg patient and his mother were subjected to clinical and molecular studies. Screening of mutations were performed in TIMM8A, TIMM13, and other mitochondrial protein transport genes by conformation sensitive gel electrophoresis (CSGE), followed by direct DNA sequencing of tissue samples from the patient. Mitochondrial DNA of the patient was also sequenced at the genes for COX subunits and some mitochondrial tRNAs. Respiratory chain activities in a muscle biopsy and cultured fibroblasts from the patient were assessed using biochemical methods. mRNA expression of TIMM8A and TIMM13 was determined by RT-PCR in cultured fibroblasts. We identified a new case of Mohr-Tranebjaerg syndrome and report the characteristics of a new pathogenic de novo mutation (c.112C>T, pGln38X) in the TIMM8A gene. Biochemical measures of respiratory chain complex activities in muscle biopsy and fibroblasts did not show a major deficiency or alteration. mRNA expression studies demonstrated increased TIMM8A mRNA levels in cultured fibroblasts from the patient. Phenotypic differences among published cases seem not to be related with the mutation location or type. Our results support the idea that dysfunctions of mitochondrial protein transport, in addition to OXPHOS deficiency, can be the basis of important mitochondrial pathologies.
 ...
PMID:Molecular genetics of a patient with Mohr-Tranebjaerg Syndrome due to a new mutation in the DDP1 gene. 1799 2

Myoclonus-dystonia (M-D) (MIM 159900) is a rare "dystonia plus" syndrome, characterized by rapid myoclonic jerks, predominantly in the neck and upper limbs, in combination with dystonia. Mutations in the gene epsilon-sarcoglycan (SGCE) are known to be responsible for approximately one-third of cases. We screened 21 probands diagnosed with M-D for large deletions who were mutation negative as determined by PCR-direct sequencing. Multiplex PCR and quantification of PCR products was performed using a modified application of denaturing high performance liquid chromatography (dHPLC). We have identified two novel large multiexonic deletions of SGCE, which were confirmed by amplifying and sequencing the deletion breakpoints. Five other families were found to harbor small mutations identified by direct sequencing. Analysis of the region surrounding the deletions demonstrates that both deletions are the result of nonhomologous recombination with homologous end joining. This is only the second report of intragenic deletions with SGCE and it highlights the need to include exonic copy number variation when performing mutational analysis of SGCE.
 ...
PMID:Large deletions account for an increasing number of mutations in SGCE. 1809 80


1 2 Next >>