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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2013
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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. |
format | Online Article Text |
id | pubmed-3815478 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
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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