Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Duplications and triplications of the alpha-synuclein (SNCA) gene have been reported in Parkinson's disease patients belonging to the Southern Swedish "Lister family". Further genealogical research has now shown that these individuals are descended from a large kindred characterized by Herman Lundborg in 1901-1913. In the expanded pedigree, a total of 25 individuals had Parkinson's disease with an autosomal dominant pattern of inheritance. Hereditary dementia, and, historically, dementia praecox have been described in other family members. Furthermore, an autosomal recessively inherited pediatric disease with nocturnal tonic-clonic fits, subsequent progressive myoclonus, startle reactions, tremor and muscle rigidity was described by Lundborg in the same pedigree. The entity was later designated Unverricht-Lundborg disease (ULD) or progressive myoclonus epilepsy type 1 (EPM1). However, Lundborg's clinical description of this disease, based on 17 patients within this kindred, differs from the modern definition of EPM1, which relies on patients with a mutation in the cystatin B (CSTB) gene. We hypothesize that the former pediatric disease, as well as the parkinsonism and dementia phenotypes, are associated with duplications, triplications and possibly higher-order multiplications of the alpha-synuclein (SNCA) gene. This hypothesis is supported by the distribution of afflicted family members within the pedigree and by recently obtained genealogical information.
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PMID:Alpha-synuclein multiplications with parkinsonism, dementia or progressive myoclonus? 1882 90

Mutations in seven genes are robustly associated with autosomal dominant (SNCA, LRRK2, EIF4G1, VPS35) or recessive (parkin/PARK2, PINK1, DJ1/PARK7) Parkinson's disease (PD) or parkinsonism. Changes in a long list of additional genes have been suggested as causes for parkinsonism or PD, including genes for hereditary ataxias (ATXN2, ATXN3, FMR1), frontotemporal dementia (C9ORF72, GRN, MAPT, TARDBP), DYT5 (GCH1, TH, SPR), and others (ATP13A2, CSF1R, DNAJC6, FBXO, GIGYF2, HTRA2, PLA2G6, POLG, SPG11, UCHL1). This review summarizes the clinical features of diseases caused by mutations in these genes, and their frequencies. Point mutations and multiplications in SNCA cause cognitive or psychiatric symptoms, parkinsonism, dysautonomia and myoclonus with widespread alpha-synuclein pathology in the central and peripheral nervous system. LRRK2 mutations may lead to a clinical phenotype closely resembling idiopathic PD with a puzzling variety in neuropathology. Mutations in parkin/PARK2, PINK1 or DJ1/PARK7 may cause early-onset parkinsonism with a low risk for cognitive decline and a pathological process usually restricted to the brainstem. Carriers of mutations in the other genes may develop parkinsonism with or without additional symptoms, but rarely a disease resembling PD. The pathogenicity of several mutations remains unconfirmed. Although some mutations occur with high frequency in specific populations, worldwide all are very rare. The genetic cause of the majority of patients with sporadic or hereditary PD remains unknown in most populations. Clinical genetic testing is useful for selected patients. Testing strategies need to be adapted individually based on clinical phenotype and estimated frequency of the mutation in the patient's population.
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PMID:Monogenic Parkinson's disease and parkinsonism: clinical phenotypes and frequencies of known mutations. 2346 81