Journal
PARKINSONISM & RELATED DISORDERS
Volume 15, Issue 7, Pages 539-541Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.parkreldis.2008.10.008
Keywords
Parkinson's disease; LRRK2; AAO; MAPT
Categories
Funding
- National Genome Network [NGFN
- 01GS0116]
- Competence Network Parkinson [01GI0201]
- Morris K. Udall Center for Excellence in Parkinson's disease Research at Mayo Clinic Jacksonville [P50 NS40256]
- Canadian Institutes of Health Research
- Canada Research Chairs program
- James & Donna-Mae Moore endowment of the Michael Smith Foundation for Health Research
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Patients with Leucine-rich repeat kinase 2 (LRRK2) linked Parkinson's disease (PD) clinically present with typical idiopathic PD. However, LRRK2-linked PD displays a pleomorphic neuropathology and high variability in age at disease onset (AAO) which suggests that environmental and/or genetic factors other than the mutation itself influence the Course of the disease. We investigated the modulation of AAO by genetic factors including the mutation-containing domain and PD associated polymorphisms in the gene coding alpha-synuclein (SNCA) and tau (MAPT) in 44 patients from 19 affected families. Using this limited number of available LRRK2 mutation carriers, we provide evidence that mutations in the kinase domain of Lrrk2 significantly decrease AAO compared to mutations in the ROC (Ras/GTPase of complex proteins) domain. Furthermore, polymorphic variations in MAPT show a significant association with AAO in individuals with LRRK2 mutations. Our results await replication in future Studies with a larger number of LRRK2 mutation carriers, but indicate an association of mutation-affected protein domain and mutation-extrinsic genetic factors with AAO and suggest that these factors could Contribute to explain the phenotypic heterogeneity observed in LRRK2-linked PD. (C) 2008 Elsevier Ltd. All rights reserved.
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