title: Alpha-synuclein p.H50Q, a novel pathogenic mutation for Parkinson's disease.
abstract: BACKGROUND
  Alpha-synuclein plays a central role in the pathophysiology of Parkinson's disease. Three missense mutations in SNCA, the gene encoding alpha-synuclein, as well as genomic multiplications have been identified as causes for autosomal-dominantly inherited Parkinsonism.
  
  
  METHODS
  Here, we describe a novel missense mutation in exon 4 of SNCA encoding a H50Q substitution in a patient with dopa-responsive Parkinson's disease with a family history of parkinsonism and dementia.
  
  
  RESULTS
  The variant was not observed in public databases or identified in unrelated subjects.
  
  
  CONCLUSIONS
  The substitution's evolutionary conservation and protein modeling provide additional support for pathogenicity as the amino acid perturbs the same amphipathic alpha helical structure as the previously described pathogenic mutations.
authors: Department of Medicine (Neurology), Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, British Columbia, Canada. silkec@mail.ubc.ca
authors: Silke
authors: S
authors: Appel-Cresswell
authors: Carles
authors: C
authors: Vilarino-Guell
authors: Mary
authors: M
authors: Encarnacion
authors: Holly
authors: H
authors: Sherman
authors: Irene
authors: I
authors: Yu
authors: Brinda
authors: B
authors: Shah
authors: David
authors: D
authors: Weir
authors: Christina
authors: C
authors: Thompson
authors: Chelsea
authors: C
authors: Szu-Tu
authors: Joanne
authors: J
authors: Trinh
authors: Jan O
authors: JO
authors: Aasly
authors: Alex
authors: A
authors: Rajput
authors: Ali H
authors: AH
authors: Rajput
authors: A
authors: A
authors: Jon Stoessl
authors: Matthew J
authors: MJ
authors: Farrer
mesh_terms: D005973:Glutamine / Q000235:genetics*; D006639:Histidine / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D010375:Pedigree; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D051844:alpha-Synuclein; D005973:Glutamine; D006639:Histidine