title: Analysis of Parkinson's disease brain-derived DNA for alpha-synuclein coding somatic mutations.
abstract: BACKGROUND
  Although alpha-synuclein (SNCA) is crucial to the pathogenesis of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), mutations in the gene appear to be rare. We have recently hypothesized that somatic mutations in early development could contribute to PD.
  
  
  METHODS
  Expanding on our recent negative small study, we used high-resolution melting (HRM) analysis to screen SNCA coding exons for somatic point mutations in DNA from 539 PD and DLB cerebellar samples, with two additional regions (frontal cortex, substantia nigra) for 20 PD cases. We used artificial mosaics to determine sensitivity where possible.
  
  
  RESULTS
  We did not detect any evidence of somatic coding mutations. Three cases were heterozygous for known silent polymorphisms. The protocol we used was sensitive enough to detect 5% to 10% mutant DNA.
  
  
  CONCLUSIONS
  Using DNA predominantly from cerebellum, but also from frontal cortex and substantia nigra (n = 20 each), we have not detected any somatic coding SNCA point mutations.
authors.affiliation: Department of Clinical Neuroscience, Institute of Neurology, University College London, London, United Kingdom.
authors.forename: Christos
authors.initials: C
authors.lastname: Proukakis
authors.forename: Maryiam
authors.initials: M
authors.lastname: Shoaee
authors.forename: James
authors.initials: J
authors.lastname: Morris
authors.forename: Timothy
authors.initials: T
authors.lastname: Brier
authors.forename: Eleanna
authors.initials: E
authors.lastname: Kara
authors.forename: Una-Marie
authors.initials: UM
authors.lastname: Sheerin
authors.forename: Gavin
authors.initials: G
authors.lastname: Charlesworth
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tolosa
authors.forename: Henry
authors.initials: H
authors.lastname: Houlden
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Wood
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Schapira
mesh_terms: D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004247:DNA / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D020961:Lewy Body Disease / Q000150:complications / Q000235:genetics / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: D051844:alpha-Synuclein; D004247:DNA
keywords: SNCA; alpha-synuclein; etiology of Parkinson's disease; mosaicism; somatic mutation
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