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Title | C9ORF72 intermediate repeat copies are a significant risk factor for Parkinson disease. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Nuytemans K, Bademci G, Kohli MM, Beecham GW, Wang L-S, Young JI, Nahab F, Martin ER, Gilbert JR, Benatar M, Haines JL, Scott WK, Züchner S, Pericak-Vance MA, Vance JM |
Journal | Ann Hum Genet |
Volume | 77 |
Issue | 5 |
Pagination | 351-63 |
Date Published | 2013 Sep |
ISSN | 1469-1809 |
Keywords | Adolescent, Adult, Aged, Aged, 80 and over, C9orf72 Protein, Case-Control Studies, Child, Gene Dosage, Genetic Predisposition to Disease, Genotype, Humans, Middle Aged, Parkinson Disease, Pedigree, Phenotype, Proteins, Repetitive Sequences, Nucleic Acid, Risk Factors, Young Adult |
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. |
DOI | 10.1111/ahg.12033 |
Alternate Journal | Ann. Hum. Genet. |
PubMed ID | 23845100 |
PubMed Central ID | PMC3815478 |
Grant List | R01AG019085 / AG / NIA NIH HHS / United States RC2 AG036528 / AG / NIA NIH HHS / United States 5P50NS071674-03 / NS / NINDS NIH HHS / United States R01AG027944-02 / AG / NIA NIH HHS / United States R01 AG019085 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States U01AG032984-02 / AG / NIA NIH HHS / United States P50 NS039764 / NS / NINDS NIH HHS / United States R01 AG028786 / AG / NIA NIH HHS / United States NS39764 / NS / NINDS NIH HHS / United States RC2AG036528 / AG / NIA NIH HHS / United States R01AG028786-02 / AG / NIA NIH HHS / United States R01 AG027944 / AG / NIA NIH HHS / United States P50 NS071674 / NS / NINDS NIH HHS / United States |