title: Absence of C9ORF72 expanded or intermediate repeats in autopsy-confirmed Parkinson's disease.
abstract: BACKGROUND
  We have reported that intermediate repeat lengths of the C9ORF72 repeat are a risk factor for Parkinson's disease (PD) in a clinically diagnosed data set. Because 10% to 25% of clinically diagnosed PD have different diagnoses upon autopsy, we hypothesized that this may reflect phenotypic heterogeneity or concomitant pathology of other neurodegenerative disorders.
  
  
  METHODS
  We screened 488 autopsy-confirmed PD cases for expansion haplotype tag rs3849942T. In 196 identified haplotype carriers, the C9ORF72 repeat was genotyped using the repeat-primed polymerase chain reaction assay.
  
  
  RESULTS
  No larger (intermediate or expanded) repeats were found in these autopsy-confirmed PD samples. This absence of larger repeats is significantly different from the frequency in clinically diagnosed datasets (P = 0.002).
  
  
  CONCLUSIONS
  Our results suggest that expanded or intermediate C9ORF72 repeats in clinically diagnosed PD or parkinsonism might be an indication of heterogeneity in clinically diagnosed PD cases. Further studies are needed to elucidate the potential contribution of the C9ORF72 repeat to autopsy-confirmed PD.
authors.affiliation: University of Miami, Miller School of Medicine, John P. Hussman Institute for Human Genomics, Miami, Florida, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Nuytemans
authors.forename: Vanessa
authors.initials: V
authors.lastname: Inchausti
authors.forename: Gary W
authors.initials: GW
authors.lastname: Beecham
authors.forename: Liyong
authors.initials: L
authors.lastname: Wang
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Mash
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Frosch
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Foroud
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Honig
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.forename: Ted M
authors.initials: TM
authors.lastname: Dawson
authors.forename: Eden R
authors.initials: ER
authors.lastname: Martin
authors.forename: William K
authors.initials: WK
authors.lastname: Scott
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Vance
mesh_terms: D001344:Autopsy / Q000379:methods*; D000073885:C9orf72 Protein; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D010300:Parkinson Disease / Q000175:diagnosis* / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins
keywords: C9ORF72 repeat; Parkinson's disease; autopsy confirmed; parkinsonism