Funding agencies: This project was supported by NS039764 and NS071674 (to G.W.B., W.K.S., E.R.M., L.W., K.N., D.M.D., and J.M.V.), P50 NS072187 and P50 AG016574 (to D.W.D.), P50 NS053488 (to J.Q.T. and V.M.-Y.L.), NeuroBioBank HHSN271201300028C (to D.C.M.), NS38377 and the JPB Foundation (to T.M.D.), P01 AG007232 (to L.S.H.), AG06781, AG005136, and NS062684 (to T.J.M.), P01 AG007232 (to L.S.H.), R01NS37167, P30AG10133, and U24AG021886 (to T.F.), and P50 AG005134 and P50 NS038372 (to M.P.F.).
Absence of C9ORF72 expanded or intermediate repeats in autopsy-confirmed Parkinson's disease
Version of Record online: 26 FEB 2014
© 2014 International Parkinson and Movement Disorder Society
Volume 29, Issue 6, pages 827–830, May 2014
How to Cite
Nuytemans, K., Inchausti, V., Beecham, G. W., Wang, L., Dickson, D. W., Trojanowski, J. Q., Lee, V. M.-Y., Mash, D. C., Frosch, M. P., Foroud, T. M., Honig, L. S., Montine, T. J., Dawson, T. M., Martin, E. R., Scott, W. K. and Vance, J. M. (2014), Absence of C9ORF72 expanded or intermediate repeats in autopsy-confirmed Parkinson's disease. Mov. Disord., 29: 827–830. doi: 10.1002/mds.25838
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
- Issue online: 6 MAY 2014
- Version of Record online: 26 FEB 2014
- Manuscript Accepted: 20 JAN 2014
- Manuscript Revised: 6 JAN 2014
- Manuscript Received: 29 OCT 2013
- autopsy confirmed;
- Parkinson's disease;
- C9ORF72 repeat;
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.
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.
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).
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. © 2014 International Parkinson and Movement Disorder Society