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

Academic Article


  • 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.
  • Authors

    Published In

  • Neurology  Journal
  • Keywords

  • C9orf72 Protein, Cohort Studies, DNA Repeat Expansion, Female, Humans, Internationality, Male, Middle Aged, Parkinson Disease, Proteins
  • Digital Object Identifier (doi)

    Author List

  • Theuns J; Verstraeten A; Sleegers K; Wauters E; Gijselinck I; Smolders S; Crosiers D; Corsmit E; Elinck E; Sharma M
  • Start Page

  • 1906
  • End Page

  • 1913
  • Volume

  • 83
  • Issue

  • 21