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C9ORF72 Intermediate Repeat Copies Are a Significant Risk Factor for Parkinson Disease

We set out to determine whether expansions in the C9ORF72 repeat found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) families are associated with Parkinson disease (PD). We determined the repeat size in a total of 889 clinically ascertained patients (including PD and essen...

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Autores principales: Nuytemans, Karen, Bademci, Güney, Kohli, Martin M, Beecham, Gary W, Wang, Liyong, Young, Juan I, Nahab, Fatta, Martin, Eden R, Gilbert, John R, Benatar, Michael, Haines, Jonathan L, Scott, William K, Züchner, Stephan, Pericak-Vance, Margaret A, Vance, Jeffery M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815478/
https://www.ncbi.nlm.nih.gov/pubmed/23845100
http://dx.doi.org/10.1111/ahg.12033
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author Nuytemans, Karen
Bademci, Güney
Kohli, Martin M
Beecham, Gary W
Wang, Liyong
Young, Juan I
Nahab, Fatta
Martin, Eden R
Gilbert, John R
Benatar, Michael
Haines, Jonathan L
Scott, William K
Züchner, Stephan
Pericak-Vance, Margaret A
Vance, Jeffery M
author_facet Nuytemans, Karen
Bademci, Güney
Kohli, Martin M
Beecham, Gary W
Wang, Liyong
Young, Juan I
Nahab, Fatta
Martin, Eden R
Gilbert, John R
Benatar, Michael
Haines, Jonathan L
Scott, William K
Züchner, Stephan
Pericak-Vance, Margaret A
Vance, Jeffery M
author_sort Nuytemans, Karen
collection PubMed
description We set out to determine whether expansions in the C9ORF72 repeat found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) families are associated with Parkinson disease (PD). We determined the repeat size in a total of 889 clinically ascertained patients (including PD and essential tremor plus Parkinsonism (ETP)) and 1144 controls using a repeat-primed PCR assay. We found that large C9ORF72 repeat expansions (>30 repeats) were not contributing to PD risk. However, PD and ETP cases had a significant increase in intermediate (>20 to 30+) repeat copies compared to controls. Overall, 14 cases (13 PD, 1 ETP) and three controls had >20 repeat copies (Fisher's exact test p = 0.002). Further, seven cases and no controls had >23 repeat copies (p = 0.003). Our results suggest that intermediate copy numbers of the C9ORF72 repeat contribute to risk for PD and ETP. This also suggests that PD, ALS and FTD share some pathophysiological mechanisms of disease. Further studies are needed to elucidate the contribution of the C9ORF72 repeat in the overall PD population and to determine whether other common genetic risk factors exist between these neurodegenerative disorders.
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spelling pubmed-38154782014-01-29 C9ORF72 Intermediate Repeat Copies Are a Significant Risk Factor for Parkinson Disease Nuytemans, Karen Bademci, Güney Kohli, Martin M Beecham, Gary W Wang, Liyong Young, Juan I Nahab, Fatta Martin, Eden R Gilbert, John R Benatar, Michael Haines, Jonathan L Scott, William K Züchner, Stephan Pericak-Vance, Margaret A Vance, Jeffery M Ann Hum Genet Original Articles We set out to determine whether expansions in the C9ORF72 repeat found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) families are associated with Parkinson disease (PD). We determined the repeat size in a total of 889 clinically ascertained patients (including PD and essential tremor plus Parkinsonism (ETP)) and 1144 controls using a repeat-primed PCR assay. We found that large C9ORF72 repeat expansions (>30 repeats) were not contributing to PD risk. However, PD and ETP cases had a significant increase in intermediate (>20 to 30+) repeat copies compared to controls. Overall, 14 cases (13 PD, 1 ETP) and three controls had >20 repeat copies (Fisher's exact test p = 0.002). Further, seven cases and no controls had >23 repeat copies (p = 0.003). Our results suggest that intermediate copy numbers of the C9ORF72 repeat contribute to risk for PD and ETP. This also suggests that PD, ALS and FTD share some pathophysiological mechanisms of disease. Further studies are needed to elucidate the contribution of the C9ORF72 repeat in the overall PD population and to determine whether other common genetic risk factors exist between these neurodegenerative disorders. Blackwell Publishing Ltd 2013-09 2013-07-12 /pmc/articles/PMC3815478/ /pubmed/23845100 http://dx.doi.org/10.1111/ahg.12033 Text en © 2013 The Authors. Annals of Human Genetics published by John Wiley & Sons Ltd/University College London http://creativecommons.org/licenses/by-nc/3.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Nuytemans, Karen
Bademci, Güney
Kohli, Martin M
Beecham, Gary W
Wang, Liyong
Young, Juan I
Nahab, Fatta
Martin, Eden R
Gilbert, John R
Benatar, Michael
Haines, Jonathan L
Scott, William K
Züchner, Stephan
Pericak-Vance, Margaret A
Vance, Jeffery M
C9ORF72 Intermediate Repeat Copies Are a Significant Risk Factor for Parkinson Disease
title C9ORF72 Intermediate Repeat Copies Are a Significant Risk Factor for Parkinson Disease
title_full C9ORF72 Intermediate Repeat Copies Are a Significant Risk Factor for Parkinson Disease
title_fullStr C9ORF72 Intermediate Repeat Copies Are a Significant Risk Factor for Parkinson Disease
title_full_unstemmed C9ORF72 Intermediate Repeat Copies Are a Significant Risk Factor for Parkinson Disease
title_short C9ORF72 Intermediate Repeat Copies Are a Significant Risk Factor for Parkinson Disease
title_sort c9orf72 intermediate repeat copies are a significant risk factor for parkinson disease
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815478/
https://www.ncbi.nlm.nih.gov/pubmed/23845100
http://dx.doi.org/10.1111/ahg.12033
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