Absence of C9ORF72 expanded or intermediate repeats in autopsy-confirmed Parkinson's disease

Karen Nuytemans, Vanessa Inchausti, Gary W. Beecham, Liyong Wang, Dennis W. Dickson, John Q. Trojanowski, Virginia M Y Lee, Deborah C. Mash, Matthew P. Frosch, Tatiana Foroud, Lawrence S. Honig, Thomas J. Montine, Ted M. Dawson, Eden R. Martin, William K. Scott, Jeffery M. Vance

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)827-830
Number of pages4
JournalMovement Disorders
Volume29
Issue number6
DOIs
StatePublished - 2014

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Parkinson Disease
Autopsy
Haplotypes
Parkinsonian Disorders
Neurodegenerative Diseases
Pathology
Polymerase Chain Reaction

Keywords

  • Autopsy confirmed
  • C9ORF72 repeat
  • Parkinson's disease
  • Parkinsonism

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Medicine(all)

Cite this

Nuytemans, K., Inchausti, V., Beecham, G. W., Wang, L., Dickson, D. W., Trojanowski, J. Q., ... Vance, J. M. (2014). Absence of C9ORF72 expanded or intermediate repeats in autopsy-confirmed Parkinson's disease. Movement Disorders, 29(6), 827-830. https://doi.org/10.1002/mds.25838

Absence of C9ORF72 expanded or intermediate repeats in autopsy-confirmed Parkinson's disease. / Nuytemans, Karen; Inchausti, Vanessa; Beecham, Gary W.; Wang, Liyong; Dickson, Dennis W.; Trojanowski, John Q.; Lee, Virginia M Y; Mash, Deborah C.; Frosch, Matthew P.; Foroud, Tatiana; Honig, Lawrence S.; Montine, Thomas J.; Dawson, Ted M.; Martin, Eden R.; Scott, William K.; Vance, Jeffery M.

In: Movement Disorders, Vol. 29, No. 6, 2014, p. 827-830.

Research output: Contribution to journalArticle

Nuytemans, K, Inchausti, V, Beecham, GW, Wang, L, Dickson, DW, Trojanowski, JQ, Lee, VMY, Mash, DC, Frosch, MP, Foroud, T, Honig, LS, Montine, TJ, Dawson, TM, Martin, ER, Scott, WK & Vance, JM 2014, 'Absence of C9ORF72 expanded or intermediate repeats in autopsy-confirmed Parkinson's disease', Movement Disorders, vol. 29, no. 6, pp. 827-830. https://doi.org/10.1002/mds.25838
Nuytemans K, Inchausti V, Beecham GW, Wang L, Dickson DW, Trojanowski JQ et al. Absence of C9ORF72 expanded or intermediate repeats in autopsy-confirmed Parkinson's disease. Movement Disorders. 2014;29(6):827-830. https://doi.org/10.1002/mds.25838
Nuytemans, Karen ; Inchausti, Vanessa ; Beecham, Gary W. ; Wang, Liyong ; Dickson, Dennis W. ; Trojanowski, John Q. ; Lee, Virginia M Y ; Mash, Deborah C. ; Frosch, Matthew P. ; Foroud, Tatiana ; Honig, Lawrence S. ; Montine, Thomas J. ; Dawson, Ted M. ; Martin, Eden R. ; Scott, William K. ; Vance, Jeffery M. / Absence of C9ORF72 expanded or intermediate repeats in autopsy-confirmed Parkinson's disease. In: Movement Disorders. 2014 ; Vol. 29, No. 6. pp. 827-830.
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AB - 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.

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