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

Theuns, J.; Verstraeten, A.; Sleegers, K.; Wauters, E.; Gijselinck, I.; Smolders, S.; Crosiers, D.; Corsmit, E.; Elinck, E. and Sharma, M., et al. (2014) In Neurology 83(21). p.13-1906
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... (More)
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. (Less)
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keywords
Cohort Studies, DNA Repeat Expansion/ genetics, Female, Humans, Internationality, Male, Middle Aged, Parkinson Disease/ diagnosis/epidemiology/ genetics, Proteins/ genetics
in
Neurology
volume
83
issue
21
pages
13 - 1906
publisher
American Academy of Neurology
external identifiers
  • scopus:84961289268
ISSN
1526-632X
DOI
10.1212/wnl.0000000000001012
language
English
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yes
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d11aeba5-d37c-4611-8218-4bebf8e63454 (old id 7374380)
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2015-06-22 10:16:28
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@article{d11aeba5-d37c-4611-8218-4bebf8e63454,
  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.},
  author       = {Theuns, J. and Verstraeten, A. and Sleegers, K. and Wauters, E. and Gijselinck, I. and Smolders, S. and Crosiers, D. and Corsmit, E. and Elinck, E. and Sharma, M. and Kruger, R. and Lesage, S. and Brice, A. and Chung, S. J. and Kim, M. J. and Kim, Y. J. and Ross, O. A. and Wszolek, Z. K. and Rogaeva, E. and Xi, Z. and Lang, A. E. and Klein, C. and Weissbach, A. and Mellick, G. D. and Silburn, P. A. and Hadjigeorgiou, G. M. and Dardiotis, E. and Hattori, N. and Ogaki, K. and Tan, E. K. and Zhao, Y. and Aasly, J. and Valente, E. M. and Petrucci, S. and Annesi, G. and Quattrone, A. and Ferrarese, C. and Brighina, L. and Deutschlander, A. and Puschmann, Andreas and Nilsson, C. and Garraux, G. and LeDoux, M. S. and Pfeiffer, R. F. and Boczarska-Jedynak, M. and Opala, G. and Maraganore, D. M. and Engelborghs, S. and De Deyn, P. P. and Cras, P. and Cruts, M. and Van Broeckhoven, C.},
  issn         = {1526-632X},
  keyword      = {Cohort Studies,DNA Repeat Expansion/ genetics,Female,Humans,Internationality,Male,Middle Aged,Parkinson Disease/ diagnosis/epidemiology/ genetics,Proteins/ genetics},
  language     = {eng},
  number       = {21},
  pages        = {13--1906},
  publisher    = {American Academy of Neurology},
  series       = {Neurology},
  title        = {Global investigation and meta-analysis of the C9orf72 (G4C2)n repeat in Parkinson disease},
  url          = {http://dx.doi.org/10.1212/wnl.0000000000001012},
  volume       = {83},
  year         = {2014},
}