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Journal of Human Genetics Jun 2016Cerebellar atrophy is recognized in various types of childhood neurological disorders with clinical and genetic heterogeneity. Genetic analyses such as whole exome...
Cerebellar atrophy is recognized in various types of childhood neurological disorders with clinical and genetic heterogeneity. Genetic analyses such as whole exome sequencing are useful for elucidating the genetic basis of these conditions. Pathological recessive mutations in Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase (SEPSECS) have been reported in a total of 11 patients with pontocerebellar hypoplasia type 2, progressive cerebellocerebral atrophy or progressive encephalopathy, yet detailed clinical features are limited to only four patients. We identified two new families with progressive cerebellar atrophy, and by whole exome sequencing detected biallelic SEPSECS mutations: c.356A>G (p.Asn119Ser) and c.77delG (p.Arg26Profs*42) in family 1, and c.356A>G (p.Asn119Ser) and c.467G>A (p.Arg156Gln) in family 2. Their development was slightly delayed regardless of normal brain magnetic resonance imaging (MRI) in infancy. The progression of clinical symptoms in these families is evidently slower than in previously reported cases, and the cerebellar atrophy milder by brain MRI, indicating that SEPSECS mutations are also involved in milder late-onset cerebellar atrophy.
Topics: Adolescent; Alleles; Amino Acid Substitution; Amino Acyl-tRNA Synthetases; Brain; Child; Child, Preschool; Exome; Female; Gene Frequency; Genotype; High-Throughput Nucleotide Sequencing; Humans; Infant; Magnetic Resonance Imaging; Male; Mutation; Olivopontocerebellar Atrophies; Pedigree; Phenotype; Polymorphism, Single Nucleotide; Sequence Analysis, DNA
PubMed: 26888482
DOI: 10.1038/jhg.2016.9 -
Acta Neuropathologica 1991A 75-year-old woman with parkinsonism plus was found at autopsy to have striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA) and intracytoplasmic...
A 75-year-old woman with parkinsonism plus was found at autopsy to have striatonigral degeneration (SND), olivopontocerebellar atrophy (OPCA) and intracytoplasmic neuronal inclusions, mostly confined to the hippocampus and pontine nuclei. These inclusions were intensely argyrophilic, ubiquitinated and expressed variable immunoreactivity for neurofilament but not for tau-1 and Alz 50 proteins. Ultrastructurally, they were formed of skeins of intermediate filaments averaging 11 nm in diameter. They were considered to represent Pick bodies. There was no cortical atrophy, gliosis or sponginess. To our knowledge, SND and OPCA in association with Pick's disease has not been previously reported. In addition, intracytoplasmic oligodendroglial inclusions were present in the deeper layers of the cortex, especially the pericentral gyri, the striatum and the white matter of certain regions of the cerebral hemispheres, as well as in the cerebellum. These inclusions which have been previously reported in multisystem atrophy, had to be distinguished from cortical Lewy bodies, Pick bodies, and the nonspecific ubiquitinated bodies in the white matter of the aged brain, mainly by their topographical distribution and immunostaining properties.
Topics: Aged; Brain; Corpus Striatum; Dementia; Female; Humans; Inclusion Bodies; Microscopy, Electron; Nerve Degeneration; Neuroglia; Olivopontocerebellar Atrophies; Spinal Cord; Staining and Labeling; Substantia Nigra
PubMed: 1711756
DOI: 10.1007/BF00305870 -
Neurology Jul 1987We studied two patients with nonfamilial olivopontocerebellar atrophy with skeletal myoclonus. Palatal or skeletal myoclonus is probably not a coincidental finding but...
We studied two patients with nonfamilial olivopontocerebellar atrophy with skeletal myoclonus. Palatal or skeletal myoclonus is probably not a coincidental finding but another manifestation of the underlying disease. In both cases, the myoclonus was suppressed by administration of trihexyphenidyl, indicating a cholinergic disorder.
Topics: Brain; Clonazepam; Drug Therapy, Combination; Electromyography; Female; Humans; Male; Middle Aged; Muscles; Myoclonus; Olivopontocerebellar Atrophies; Spinocerebellar Degenerations; Tomography, X-Ray Computed; Trihexyphenidyl
PubMed: 3474546
DOI: 10.1212/wnl.37.7.1258 -
Brain Research Jul 1995Four neuropeptides; cerebellin, corticotropin-releasing hormone (CRH), neuropeptide Y and somatostatin were studied by radioimmunoassay in the postmortem human brains...
Four neuropeptides; cerebellin, corticotropin-releasing hormone (CRH), neuropeptide Y and somatostatin were studied by radioimmunoassay in the postmortem human brains obtained from three patients with olivopontocerebellar atrophy (OPCA) and one with Shy-Drager syndrome. Significant decreases in cerebellin and CRH concentrations were found in the cerebellar hemisphere of these diseases compared with controls. These findings suggest important pathophysiological roles of cerebellin and CRH in these cerebellar diseases. Such significant decreases were not found in neuropeptide Y and somatostatin.
Topics: Adult; Aged; Cerebellum; Corticotropin-Releasing Hormone; Female; Humans; Male; Middle Aged; Nerve Tissue Proteins; Neuropeptide Y; Olivopontocerebellar Atrophies; Radioimmunoassay; Shy-Drager Syndrome; Somatostatin
PubMed: 7583264
DOI: 10.1016/0006-8993(95)00467-5 -
The Journal of the Association of... Aug 2003The spectrum of degenerative ataxia includes the symptomatic degenerative ataxias and the primary degenerative ataxias. The later may be sporadic and idiopathic or...
The spectrum of degenerative ataxia includes the symptomatic degenerative ataxias and the primary degenerative ataxias. The later may be sporadic and idiopathic or hereditary, being genetically determined. When an individual ataxic patient presents with an adult-onset degenerative ataxia and has a negative family history, the physician is faced with a diagnosis of pure idiopathic sporadic degenerative ataxia or one of the hereditary ataxias. The clinical spectrum of olivopontocerebellar atrophy (OPCA) usually consists of pancerebellar signs with pyramidal and abnormal eye movements. Although Stridor is more commonly found in multisystem atrophy, it is rarely seen in OPCA. We, here report a case of third decade onset of ataxia presenting with stridor.
Topics: Cerebellum; Diagnosis, Differential; Humans; Male; Middle Aged; Muscle, Skeletal; Neuropsychological Tests; Olivopontocerebellar Atrophies; Pyramidal Tracts; Respiratory Sounds; Spinocerebellar Degenerations
PubMed: 14651147
DOI: No ID Found -
Movement Disorders : Official Journal... 1992Machado-Joseph disease is an autosomal dominant spinocerebellar degeneration. It expresses itself clinically with variable expression. Type one patients have early onset... (Review)
Review
Machado-Joseph disease is an autosomal dominant spinocerebellar degeneration. It expresses itself clinically with variable expression. Type one patients have early onset with a rapid progression of symptoms including spasticity, rigidity and myokymia. Type two patients are the most common phenotype with ataxia and spasticity. Type three patients develop progressive ataxia with variable amyotrophy. All patients have ophthalmoparesis and normal mental status. The neuropathology consists of neuronal loss and gliosis in the substantia nigra, motor cranial nuclei, dentate nucleus of the cerebellum, and variable neuronal loss with gliosis in the cerebellar cortex and neostriatum. The cerebral cortex is normal histologically. The inferior olivary nuclei are normal, thus separating this disease from olivopontocerebellar atrophy (OPCA). The disease has a worldwide distribution including families described in Portugal, the Azores, Spain, Italy, United States, Canada, Brazil, China, Taiwan, and Japan. The gene has not been mapped for this disease but the locus on chromosome 6p mapped for most families with OPCA has been excluded for this disorder.
Topics: Chromosome Aberrations; Chromosome Disorders; Genes, Dominant; Genetics, Population; Humans; Neurologic Examination; Olivopontocerebellar Atrophies; Pedigree; Phenotype; Spinocerebellar Degenerations
PubMed: 1620135
DOI: 10.1002/mds.870070302 -
Acta Neuropathologica Aug 2005We report a 57-year-old woman with multiple system atrophy (MSA) of 15-month duration. The patient developed dysarthria, followed by impaired balance of gait, mild limb...
We report a 57-year-old woman with multiple system atrophy (MSA) of 15-month duration. The patient developed dysarthria, followed by impaired balance of gait, mild limb ataxia, and saccadic eye movement. A postmortem examination performed after she was found dead in a bathtub revealed neuronal loss restricted to the olivopontocerebellar system, being more severe in the pontine nucleus. Mild neuronal loss was also found in the anterior vermis and inferior olivary nucleus. Alpha-synuclein immunohistochemistry demonstrated widespread occurrence of glial cytoplasmic inclusions in the central nervous system, which were more numerous in the pontine base and cerebellar white matter. In contrast, neuronal alpha-synuclein accumulation was confined to the pontine and inferior olivary nuclei. The number of neuronal intranuclear inclusions was much higher than that of neuronal cytoplasmic inclusions. Moreover, alpha-synuclein accumulation was more severe in the neurites than in the cytoplasm or nucleus. This case demonstrates the early pattern of brain pathology in MSA-cerebellar (olivopontocerebellar atrophy).
Topics: Brain; Female; Humans; Immunohistochemistry; Inclusion Bodies; Middle Aged; Neurons; Olivopontocerebellar Atrophies; alpha-Synuclein
PubMed: 15971057
DOI: 10.1007/s00401-005-1029-1 -
Journal of the Neurological Sciences May 1993We examined the cerebral cortices of six brains from patients with sporadic olivopontocerebellar atrophy (s-OPCA), five control brains including four from patients who...
We examined the cerebral cortices of six brains from patients with sporadic olivopontocerebellar atrophy (s-OPCA), five control brains including four from patients who had died without neurological disease, and one from a patient with Holmes-type cerebellar cortical atrophy. Distinct laminar astrocytosis of the motor cortices in the fifth layer were demonstrated in 4 of 6 s-OPCA cases and in none of the control cases by immunohistochemistry for glial fibrillary acidic protein. The astrocytosis localized in the primary motor cortex and its distribution pattern were clearly different from those of so-called glial cytoplasmic inclusion. This cortical astrocytosis appears to be characteristic of s-OPCA and may reflect the pathology of the primary motor cortex.
Topics: Aged; Antibodies, Monoclonal; Astrocytes; Cerebral Cortex; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Inclusion Bodies; Male; Middle Aged; Neuroglia; Oligodendroglia; Olivopontocerebellar Atrophies; Organ Specificity
PubMed: 8251013
DOI: 10.1016/0022-510x(93)90087-f -
Acta Neuropathologica May 2013Corticobasal degeneration (CBD) is a disorder affecting cognition and movement due to a progressive neurodegeneration associated with distinctive neuropathologic...
Corticobasal degeneration (CBD) is a disorder affecting cognition and movement due to a progressive neurodegeneration associated with distinctive neuropathologic features, including abnormal phosphorylated tau protein in neurons and glia in cortex, basal ganglia, diencephalon, and brainstem, as well as ballooned neurons and astrocytic plaques. We identified three cases of CBD with olivopontocerebellar atrophy (CBD-OPCA) that did not have α-synuclein-positive glial cytoplasmic inclusions of multiple system atrophy (MSA). Two patients had clinical features suggestive of progressive supranuclear palsy (PSP), and the third case had cerebellar ataxia thought to be due to idiopathic OPCA. Neuropathologic features of CBD-OPCA are compared to typical CBD, as well as MSA and PSP. CBD-OPCA and MSA had marked neuronal loss in pontine nuclei, inferior olivary nucleus, and Purkinje cell layer. Neuronal loss and grumose degeneration in the cerebellar dentate nucleus were comparable in CBD-OPCA and PSP. Image analysis of tau pathology showed greater infratentorial tau burden, especially in pontine base, in CBD-OPCA compared with typical CBD. In addition, CBD-OPCA had TDP-43 immunoreactive neuronal and glial cytoplasmic inclusions and threads throughout the basal ganglia and in olivopontocerebellar system. CBD-OPCA met neuropathologic research diagnostic criteria for CBD and shared tau biochemical characteristics with typical CBD. These results suggest that CBD-OPCA is a distinct clinicopathologic variant of CBD with olivopontocerebellar TDP-43 pathology.
Topics: Aged; Cerebellar Ataxia; DNA-Binding Proteins; Female; Humans; Male; Nerve Degeneration; Olivopontocerebellar Atrophies; Supranuclear Palsy, Progressive
PubMed: 23371366
DOI: 10.1007/s00401-013-1087-8 -
Nihon Rinsho. Japanese Journal of... Nov 1993Sporadic olivopontocerebellar atrophy (OPCA), Shy-Drager syndrome (SDS), striatonigral degeneration (SND) are classified as multiple system atrophy (MSA), based on their... (Review)
Review
Sporadic olivopontocerebellar atrophy (OPCA), Shy-Drager syndrome (SDS), striatonigral degeneration (SND) are classified as multiple system atrophy (MSA), based on their clinicopathological findings. These clinical features, neuroimaging including CT, MRI, PET and SPECT findings, autonomic function test, pathological findings and treatments are reviewed. Several advances such as noradrenaline loading test, low signal intensity on T2 weighted image on super-conductive MRI and glial cytoplasmic inclusions in the central nervous system on pathological finding are notable. However, unsatisfactory medical treatment for MSA must be resolved in a near future.
Topics: Autonomic Nervous System; Corpus Striatum; Electrophysiology; Female; Humans; Nerve Degeneration; Olivopontocerebellar Atrophies; Shy-Drager Syndrome; Substantia Nigra
PubMed: 8277576
DOI: No ID Found