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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inherited ataxias and hereditary spastic paraplegias are two heterogeneous groups of neurodegenerative disorders with a wide spectrum of clinical symptoms and also, with a remarkable number of involved loci/genes. Inherited ataxias are clinically characterized by progressive degeneration of cerebellum and spinocerebellar tracts of the spinal cord associated with a variable combination of signs of central and peripheral nervous system. Hereditary spastic paraplegias (HSPs) are characterized by slowly progressive spasticity and weakness of lower limbs, due to pyramidal tract dysfunction. The classification of these diseases is extremely difficult because of overlapping symptoms among different clinical forms. For this reason, the genetic classification for both inherited ataxias and HSP forms, based on the causative loci/genes has reached general acceptance. The aim of this review is to summarize the genetics and the pathogenic mechanisms involved in these two groups of neurodegenerative spinocerebellar disorders.
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PMID:Genetics and pathogenesis of inherited ataxias and spastic paraplegias. 2022 32

Hereditary spastic paraplegia (HSP) is a neurodegenerative disease characterized by progressive spasticity in the lower extremities. Mutations in the atlastin GTPase 1 (ATL1) gene cause approximately 10% of autosomal dominantly inherited HSP. For many subjects with an ATL1 mutation, spastic gait begins in early childhood and does not significantly worsen, even over many years; such cases resemble spastic diplegic cerebral palsy. Herein we report a heterozygous R239C mutation in the ATL1 gene in a Korean family. The family members exhibited early onset pure spastic paraplegia and had been previously diagnosed with the diplegic form of cerebral palsy. We suggest that spastic paraplegia type 3 (SPG3A) be included in the differential diagnosis of early onset spastic paraplegia. To the best of our knowledge, this is the first report of a genetically confirmed family affected with SPG3A in Korea.
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PMID:Clinical and genetic analysis of a Korean family with hereditary spastic paraplegia type 3. 2094 13

Hereditary spastic paraplegia (HSP) represents a large group of neurological disorders characterized by progressive spasticity of the lower limbs. One subtype of HSP shows an autosomal recessive form of inheritance with thin corpus callosum (ARHSP-TCC), and displays genetic heterogeneity with four known loci. We identified a consanguineous Egyptian family with five affected individuals with ARHSP-TCC. We found linkage to the SPG11 locus and identified a novel homozygous p.Q498X stop codon mutation in exon 7 in the SPG11 gene encoding Spatacsin. Cognitive impairment and polyneuropathy, reported as frequent in SPG11, were not evident. This family supports the importance of SPG11 as a frequent cause for ARHSP-TCC, and expands the clinical SPG11 spectrum.
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PMID:Expanding the clinical spectrum of SPG11 gene mutations in recessive hereditary spastic paraplegia with thin corpus callosum. 2097 Dec 20

Hereditary spastic paraplegia (HSP) designates a group of genetic disorders typically leading to spasticity in the lower limbs and consequently to gait disorders. Although the symptoms are similar to those of cerebral palsy (CP), the correct diagnosis is important for treatment recommendations as one condition is progressive in nature whereas the other is not. Due to the heterogeneity of HSP, genetic testing is complex and in some genetic forms still not possible. The aim of this study was, therefore, to investigate if instrumented 3D-gait analysis could help distinguish between these two conditions. The gait pattern of 29 patients with HSP was compared with that of 29 patients with CP who were matched in age, sex, and the extent of gait disturbance and also to 29 typically developing subjects for reference. More than 3000 gait parameters were evaluated for their relevance to classify patients into diagnostic groups. Cluster analysis revealed that these gait features may classify only subgroups of symptoms as the gait pattern is very heterogeneous within each diagnosis group. However, prolonged hip extension, knee extension, and ankle plantar flexion were identified as indicators for HSP. In addition, large trunk tilt velocities appear unique in some cases of HSP. These indicators in gait pattern may contribute in establishing the diagnosis of HSP, which is important in predicting outcome when planning surgical treatment for functional improvements in these patients.
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PMID:Gait analysis may help to distinguish hereditary spastic paraplegia from cerebral palsy. 2133 Jan 36

The hereditary spastic paraplegias (HSP) are a heterogeneous group of genetic neurodegenerative disorders in which the main feature is progressive spasticity of the lower limbs due to pyramidal tract dysfunction. Clinically HSP are divided into two forms: a pure form that presents with progressive lower limb spasticity and weakness, sensory signs and bladder dysfunction, and a complicated form, associated with more extensive neurological and extra neurological signs as well as pathological findings on brain imaging. The clinical variability observed in HSP is supported by the large underlying genetic heterogeneity. Hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is a frequent subtype of complicated HSP clinically characterized by a slowly progressive spastic paraparesis with cognitive impairment and thin corpus callosum (TCC). SPG11, the most frequent gene associated with HSP-TCC, encodes spatacsin, a protein of unknown function. We describe two siblings from an Arabic consanguineous family with slowly progressive spastic paraparesis, mental retardation, seizures, thin corpus callosum and periventricular white matter abnormalities. Homozygosity mapping identified a novel single candidate region of 7.3 Mb on chromosome 1p13.2-1p12. The finding of a new locus for AR-HSP-TCC further demonstrates the extensive genetic heterogeneity of this condition.
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PMID:A new locus (SPG47) maps to 1p13.2-1p12 in an Arabic family with complicated autosomal recessive hereditary spastic paraplegia and thin corpus callosum. 2144 Feb 62

Hereditary spastic paraplegias (HSPs) are a group of neurological disorders characterized clinically by spasticity of lower limbs and pathologically by degeneration of the corticospinal tract. Troyer syndrome is an autosomal recessive HSP caused by a frameshift mutation in the spartin (SPG20) gene. Previously, we established that this mutation results in a lack of expression of the truncated mutant spartin protein. Spartin is involved in many cellular processes and associates with several intracellular organelles, including mitochondria. Spartin contains a conserved plant-related senescence domain at its C-terminus. However, neither the function of this domain nor the roles of spartin in mitochondrial physiology are currently known. In this study, we determined that the plant-related senescence domain of spartin interacts with cardiolipin but not with two other major mitochondrial phospholipids, phosphatidylcholine and phosphatidylethanolamine. We also found that knockdown of spartin by small interfering RNA in a human neuroblastoma cell line resulted in depolarization of the mitochondrial membrane. In addition, depletion of spartin resulted in a significant decrease in both mitochondrial calcium uptake and mitochondrial membrane potential in cells treated with thapsigargin. Our results suggest that impairment of mitochondrial calcium uptake might contribute to the neurodegeneration of long corticospinal axons and the pathophysiology of Troyer syndrome.
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PMID:SPG20 protein spartin associates with cardiolipin via its plant-related senescence domain and regulates mitochondrial Ca2+ homeostasis. 2155 43

Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder defined clinically by progressive lower limb spasticity and weakness. HSP is a genetically highly heterogeneous condition with at least 46 gene loci identified so far, involving X-linked, autosomal recessive (AR) and autosomal dominant inheritance. For correct diagnosis, molecular testing is essential because clinical parameters by themselves are not reliable to differentiate HSP forms. The purpose of this study was to establish amplicon-based high-throughput genotyping for AR-HSP. A sample of 187 index cases with apparently sporadic or recessive spastic paraplegia were analyzed by applying an array-based amplification strategy. Amplicon libraries of the CYP7B1-(SPG5) and SPG7-gene were generated followed by a pooled next-generation sequencing (NGS) approach. We identified three SPG5 and seven SPG7 patients. All had one homozygous or two heterozygous mutations. In total, 20 distinct mutations (CYP7B1,n = 4and SPG7,n = 16) including two novel CYP7B1 mutations (p.G51R and p.E211KfsX3) and eight novel SPG7 mutations (p.Leu8delinsLeuLeu, p.W29X, p.R139X, p.R247X, p.G344D, p.Leu346_Leu347ins11, p.R398X and p.R398Q) were detected by this comprehensive genetic testing. Our study illustrates how amplicon-based NGS can be used as an efficient tool to study genotypes and mutations in large patient cohorts and complex phenotypes.
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PMID:Amplicon-based high-throughput pooled sequencing identifies mutations in CYP7B1 and SPG7 in sporadic spastic paraplegia patients. 2162 69

Hereditary Spastic Paraplegia (HSP) is a clinically and genetically heterogeneous group of neurological disorders that are characterized by progressive spasticity of the lower extremities. We describe an extended consanguineous Saudi family in which HSP is linked to SPG18, a previously reported autosomal recessive locus, and show that it is associated with a nullimorphic deletion of ERLIN2, a component of endoplasmic reticulum associated degradation. This finding adds to the growing diversity of cellular functions that are now known to be involved in the maintenance of the corticospinal tract neurons.
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PMID:A nullimorphic ERLIN2 mutation defines a complicated hereditary spastic paraplegia locus (SPG18). 2179 90

Hereditary spastic paraplaegias are a group of clinically and genetically heterogeneous neurodegenerative disorders characterised by progressive spasticity and weakness in the lower limbs. The most common forms of hereditary spastic paraplaegia are SPG4 and SPG3A caused by sequence variants in the SPAST and ATL1 genes, as well as by deletions and duplications not detected by standard techniques. In this study, we used the multiplex ligation-dependent probe amplification (MLPA) analysis for screening 93 patients (52 familial and 41 isolated cases). As a result, we identified 11 different deletions and 1 duplication in the SPAST gene and a single exon deletion in the ATL1 gene. These results indicate that micro-rearrangements in the SPAST gene are a fairly frequent cause of hereditary spastic paraplaegia and that MLPA is a useful and efficient technique to detect a considerable proportion of the mutations in the most common forms of hereditary spastic paraplaegias.
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PMID:Screening for the hereditary spastic paraplaegias SPG4 and SPG3A with the multiplex ligation-dependent probe amplification technique in a large population of affected individuals. 2220 32

The Japan Spastic Paraplegia Research Consortium (JASPAC) is conducting a nationwide clinical and genetic survey of patients with HSP in Japan. To date (July 20, 2011), 375 index patients with HSP from 42 prefectures in Japan have been registered. In 148 Japanese ADHSP families, SPG4 was the most common form, accounting for 47%, followed by SPG31 (4%), SPG3A (3%), SPG8 (1%), and SPG10 (1%). Meanwhile, preliminary data showed that SPG11 and ARSACS were common in Japanese ARHSP families. Since the genes in approximately 40% of ADHSP and 80% of ARHSP cases remain unknown, we aim to identify the new genes responsible for HSP. We are now searching for a novel gene responsible for ARHSP with optic atrophy and neuropathy. To date, non-Quebec patients with ARSACS have been found in the Mediterranean area, Europe and Japan. Although Quebec patients show a homogeneous phenotype, Japanese patients exhibit some atypical clinical features, as follows: slightly later onset than that in Quebec patients, absence of retinal hypermyelination, intellectual impairment, and lack of spasticity. Recently, we found characteristic MRI findings in eight Japanese ARSACS patients, who all exhibited linear hypointensity in the pons and a hypointense area in the middle cerebellar peduncles in T(2) weighted and FLAIR images.
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PMID:[Hereditary spastic paraplegia in Japan]. 2227 6


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