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Title
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Global investigation and meta-analysis of the C9orf72 repeat in Parkinson disease
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Author
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Abstract
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| Objectives: The objective of this study is to clarify the role of (G4C2)n expansions in the etiology of Parkinson disease (PD) in the worldwide multicenter Genetic Epidemiology of Parkinson's Disease (GEO-PD) cohort. Methods: C9orf72 (G4C2)n repeats were assessed in a GEO-PD cohort of 7,494 patients diagnosed with PD and 5,886 neurologically healthy control individuals ascertained in Europe, Asia, North America, and Australia. Results: A pathogenic (G4C2)n>60 expansion was detected in only 4 patients with PD (4/7,232; 0.055%), all with a positive family history of neurodegenerative dementia, amyotrophic lateral sclerosis, or atypical parkinsonism, while no carriers were detected with typical sporadic or familial PD. Meta-analysis revealed a small increase in risk of PD with an increasing number of (G4C2)n repeats; however, we could not detect a robust association between the C9orf72 (G4C2)n repeat and PD, and the population attributable risk was low. Conclusions: Together, these findings indicate that expansions in C9orf72 do not have a major role in the pathogenesis of PD. Testing for C9orf72 repeat expansions should only be considered in patients with PD who have overt symptoms of frontotemporal lobar degeneration/amyotrophic lateral sclerosis or apparent family history of neurodegenerative dementia or motor neuron disease. |
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Language
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English
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Source (journal)
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Neurology / American Academy of Neurology. - Minneapolis, Minn
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Publication
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Minneapolis, Minn
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2014
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ISSN
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0028-3878
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DOI
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10.1212/WNL.0000000000001012
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Volume/pages
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83
:21
(2014)
, p. 1906-1913
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ISI
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000345301000007
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Full text (Publisher's DOI)
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Full text (open access)
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