Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0233565 (bradykinesia)
 2,352 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a family of Japanese origin that has five individuals from two generations affected by an illness characterized by dementia, a stooped posture and an antiflexion gait with an onset in the fourth or fifth decade of life. Two siblings had a clinical phenotype characterized by dementia and Parkinsonism with stooped posture, rigidity and bradykinesia. Neuropathological alterations in both patients included numerous 'cotton wool' plaques (CWPs), senile plaques, severe amyloid angiopathy, neurofibrillary tangles, neuronal rarefaction and gliosis. CWPs were present throughout the cerebral cortex as well as in the caudate nucleus, putamen, claustrum, thalamus, substantia innominata and colliculi. These plaques contained a small quantity of argyrophilic and tau-immunopositive neurites as well as glial fibrillary acidic protein-immunopositive elements. They were mildly fluorescent with thioflavin S and immunopositive using monoclonal antibodies recognizing amyloid beta (A beta) ending at residue 42. The main constituents of CWPs were neuropil elements and extracellular amyloid fibrils. These neuropil elements were small dendrites including spines, axon terminals containing synaptic vesicles and astrocytic processes. Dendrites occasionally contained bundles of paired helical filaments. Dendrites and axons often had an irregular outline and appeared as degenerating osmiophilic processes containing electron-dense mitochondria. Genetic analysis of the proband's affected sibling revealed a novel nucleotide substitution (G to A) in exon 8 of the Presenilin 1 ( PSEN1) gene. This nucleotide change results in a glycine to aspartic acid substitution at residue 217 of the PSEN1 protein. This study provides further evidence of clinical and pathological heterogeneity in dementing illnesses associated with PSEN1 mutations.
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PMID:A novel mutation (G217D) in the Presenilin 1 gene ( PSEN1) in a Japanese family: presenile dementia and parkinsonism are associated with cotton wool plaques in the cortex and striatum. 1211 59

Corticobasal syndrome (CBS) is a clinical syndrome presenting with progressive asymmetric bradykinesia, rigidity, and dystonia accompanied by cortical signs, such as apraxia, alien limb phenomena, cortical sensory loss, myoclonus, and mirror movements. CBS is associated with different pathological conditions including FTLD-tau (corticobasal degeneration, CBD; progressive supranuclear palsy, PSP: and Pick disease), FTLD-TDP, Alzheimer disease, Creutzfeldt-Jakob disease, and Parkinson disease/dementia with Lewy bodies. Among these, the most common pathology is CBD. In patients with familial and sporadic FTLD, MAPT, GRN and C9orf72 mutations are the three main causes of the disease, even though the C9orf72 mutation is rare in Japan. Patients with MAPT mutations present with FTLD-tau, and patients with GRN and C9orf72 mutations exhibit FTLD-TDP. FTLD is also associated with VCP, CHMP2B, TARDBP and FUS mutations, but each of these account for <1% of familial FTLD cases. In sporadic cases, the H1c haplotype and the rare p.A152T variant of MAPT are known to be associated with FTLD-tau, and the common genetic variant (rs5848) in the 3'-UTR of GRN is associated with FTLD-TDP. A recent genome-wide association study identified TMEM106B as a potential risk-modifying factor for FTLD-TDP, and STX6, EIF2AK3 and MOBP, for PSP. Despite major advances in genetic studies in recent years, the majority of sporadic CBS cases are genetically unsolved. Further studies are needed to unveil the genetic background of CBS. In this review, we discuss the recent advances related to the genetics of CBS, particularly about the genetics of FTLD.
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PMID:[The genetics of corticobasal syndrome]. 2330 Jan