Format

Send to

Choose Destination
Ann Hum Genet. 2013 Sep;77(5):351-63. doi: 10.1111/ahg.12033. Epub 2013 Jul 12.

C9ORF72 intermediate repeat copies are a significant risk factor for Parkinson disease.

Author information

1
University of Miami, Miller School of Medicine, John P. Hussman Institute for Human Genomics, Biomedical Research building, 1501 NW 10th Ave, Miami, FL, 33136, USA.

Abstract

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.

KEYWORDS:

C9ORF72 repeat; Parkinson disease; association; risk factor

PMID:
23845100
PMCID:
PMC3815478
DOI:
10.1111/ahg.12033
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center