Showing papers by "Ruth H. Walker published in 2002"
TL;DR: A mutation in the ε‐sarcoglycan gene (SGCE) in most families and in the DRD2 and DYT1 genes in two single families is found and in both of the latter families a mutation of SGCE is found.
Abstract: Myoclonus-dystonia is a movement disorder associated with mutations in the epsilon-sarcoglycan gene (SGCE) in most families and in the DRD2 and DYT1 genes in two single families. In both of the latter families, we also found a mutation of SGCE. The molecular mechanisms through which the detected mutations may contribute to myoclonus-dystonia remain to be determined.
98 citations
TL;DR: Cognitive deficits may be associated with M-D, a movement disorder with involuntary jerks and dystonic contractions, and psychiatric abnormalities correlate with the motor symptoms in affected individuals.
Abstract: Background: Myoclonus-dystonia (M-D) is a movement disorder with involuntary jerks and dystonic contractions. Autosomal dominant alcohol-responsive M-D is associated with mutations in the e-sarcoglycan gene ( SGCE ) (six families) and with a missense change in the D2 dopamine receptor ( DRD2) gene (one family). Objective: To investigate the clinical phenotype associated with M-D including motor symptoms, psychiatric disorders, and neuropsychological deficits. Methods: Fifty individuals in three M-D families were evaluated and a standardized neurologic examination and DNA analysis were performed. Psychiatric profiles were established with the Diagnostic Interviews for Genetic Studies (DIGS) and the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Cognition was evaluated with standardized neuropsychological tests. Results: Distinct truncating mutations in the SGCE gene were identified in each family. Additionally, a missense alteration in the DRD2 gene was previously found in one family. Motor expression was variable, with onset of myoclonus or dystonia or both affecting the upper body and progression to myoclonus and dystonia in most cases. Psychiatric profiles revealed depression, obsessive-compulsive disorder, substance abuse, anxiety/panic/phobic disorders, and psychosis in two families, and depression only in the third family. Averaged scores from cognitive testing showed impaired verbal learning and memory in one family, impaired memory in the second family, and no cognitive deficits in the third family. Conclusions: Cognitive deficits may be associated with M-D. Psychiatric abnormalities correlate with the motor symptoms in affected individuals. Assessment of additional M-D families with known mutations is needed to determine whether these are characteristic phenotypic manifestations of M-D.
84 citations
TL;DR: No evidence was found for alterations of Immunoreactivity at the light microscopic level, specifically neither cytoplasmic aggregations nor colocalization of torsinA immunoreactivity with a marker for endoplasmic reticulum, which contrast with results of recent cell culture studies of tORSinA.
Abstract: A mutation of the DYT1 gene, which codes for torsinA, has been identified as the cause of one form of autosomal dominantly inherited dystonia. TorsinA immunohistochemistry was used to examine a case of DYT1, and several cases of non-DYT1, dystonia. No evidence was found for alterations of immunoreactivity at the light microscopic level, specifically neither cytoplasmic aggregations nor colocalization of torsinA immunoreactivity with a marker for endoplasmic reticulum. These findings contrast with results of recent cell culture studies of torsinA.
76 citations
TL;DR: This family extends the genetic spectrum of chorea-acanthocytosis to include autosomal dominant inheritance, possibly due to expanded trinucleotide repeats and intraneuronal inclusion bodies have recently been associated with a wide range of inherited neurodegenerative disorders.
Abstract: Background: The term chorea-acanthocytosis describes a heterogeneous group of neurodegenerative disorders with variable clinical features and modes of inheritance. The characteristic acanthocytic appearance of red blood cells is attributed to abnormalities of a membrane protein, band 3, although the relationship between this and the neurodegenerative process has yet to be determined. Objective: To describe features of phenotype, inheritance, and neuropathological findings in a family with this disorder. Methods: Clinical and hematologic evaluations were performed on all available family members and neuropathological examination was performed on one case. Results: Autosomal dominant inheritance was evident, with variable clinical features of chorea or parkinsonism, marked cognitive changes, but no seizures or peripheral neurologic abnormalities. Abnormalities of band 3 were demonstrated on gel electrophoresis of red blood cell membranes. Neuropathological examination revealed severe neuronal loss of the caudate-putamen and intranuclear inclusion bodies in many areas of the cerebral cortex. These inclusion bodies were immunoreactive for ubiquitin, expanded polyglutamine repeats, and torsinA. Conclusions: This family extends the genetic spectrum of chorea-acanthocytosis to include autosomal dominant inheritance, possibly due to expanded trinucleotide repeats. Intraneuronal inclusion bodies have recently been associated with a wide range of inherited neurodegenerative disorders and may provide a clue to etiopathogenesis, in addition to potentially indicating a function of torsinA.
61 citations
TL;DR: A sib-pair with a tau P301L mutation, unlike most previous cases with this mutation, parkinsonism, rather than dementing features were the predominant and presenting feature and it was observed that the P 301L mutation has occurred on the H1 tau haplotype background.
15 citations
TL;DR: A 44‐year-old patient with severe generalized childhood‐onset dystonia and macrocephaly underwent neurological evaluation and neuropathological examination, which showed severe bilateral putaminal degeneration, which subsequently correlated with the neuro Pathological findings of gliosis, spongiform degeneration and cavitation.
Abstract: Putaminal lesions of a variety of etiologies may cause secondary dystonia. We report on a case of primary putaminal degeneration as a cause of severe childhood-onset generalized dystonia and review the literature of the pathology of dystonia. A 44-year-old patient with severe generalized childhood-onset dystonia and macrocephaly underwent neurological evaluation and neuropathological examination. Neurological examination was normal apart from dystonia and signs referable to prior cryothalamotomy. Workup for metabolic and genetic causes of dystonia was negative. Neuroimaging showed severe bilateral putaminal degeneration, which subsequently correlated with the neuropathological findings of gliosis, spongiform degeneration, and cavitation. The substantia nigra pars compacta contained a normal number of neurons but decreased tyrosine hydroxylase immunoreactivity. There were no histopathological markers of other metabolic or degenerative diseases.
9 citations
01 Jan 2002
TL;DR: TorsinA may play a universal role throughout the brain, with the DYT1 mutation interfering with the function of a specific subset of neurons, which is not reflected in alterations in immunohistochemistry at the light microscope level.
Abstract: A mutation of the DYT1 gene, which codes for torsinA, has been identified as the cause of one form of autosomal-dominantly inherited dystonia. We used a recently-developed polyclonal antibody to examine torsinA immunohistochemistry in the brain of a patient with generalised DYT1 dystonia and in several cases of non-DYT1 dystonia. We found no evidence of alterations of torsinA immunoreactivity at thse light microscopic level, specifically no cytoplasmic aggregations nor co-localisation of torsinA immunoreactivity with a marker for endoplasmic reticulum. These findings contrast with results of recent cell culture studies of torsinA. Electron microscopic examination of patus monkey brain immunolabelled for torsinA confirmed the presence of torsinA in the neuronal nucleus, in nerve terminals and also in axons. TorsinA may play a universal role throughout the brain, with the DYT1 mutation interfering with the function of a specific subset of neurons, which is not reflected in alterations in immunohistochemistry at the light microscope level.
3 citations