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Neurology. 2014 Nov 18;83(21):1906-13. doi: 10.1212/WNL.0000000000001012. Epub 2014 Oct 17.

Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease.

Author information

1
Authors' affiliations are listed at the end of the article.
2
Authors' affiliations are listed at the end of the article. christine.vanbroeckhoven@molgen.vib-ua.be.

Abstract

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.

PMID:
25326098
PMCID:
PMC4248456
DOI:
10.1212/WNL.0000000000001012
[Indexed for MEDLINE]
Free PMC Article

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