1. Comprehensive Screening of a North American Parkinson’s Disease Cohort for LRRK2 Mutation
- Author
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Kelly D. Foote, Robert L. Nussbaum, Cynthia Crews, Coro Paisán-Ruiz, Sharon Reimsnider, Michael S. Okun, Grisel Lopez, Hubert H. Fernandez, E. Whitney Evans, Katrina Gwinn-Hardy, Aideen M. McInerney-Leo, Anthony Crawley, Angela Britton, Andrew B. Singleton, Roniel Malkani, Janel O. Johnson, Ronald J. Mandel, and Shushant Jain
- Subjects
Genetics ,Mutation ,Parkinson's disease ,Parkinsonism ,Biology ,medicine.disease_cause ,medicine.disease ,LRRK2 ,nervous system diseases ,Exon ,Neurology ,Cohort ,medicine ,Missense mutation ,Neurology (clinical) ,Family history - Abstract
Background: Recently, mutations in LRRK2 encoding the protein dardarin have been linked to an autosomal dominant form of parkinsonism. Objective: To identify mutations causing Parkinson’s disease (PD) in a cohort of North Americans with familial PD. Methods: We sequenced exons 1–51 of LRRK2 in 79 unrelated North American PD patients reporting a family history of the disease. Results: One patient had a missense mutation (Thr2356Ile) while two others had the common Gly2019Ser mutation. In addition, 1 patient had a 4-bp deletion in close proximity to the exon 19 splice donor (IVS20+4delGTAA) that in vitro abrogates normal splicing. Conclusions: Our observations in the 79 North American patients indicate that mutations in LRRK2 are associated with approximately 5% of PD cases with a positive family history. The results also show that G2019S represents approximately half of the LRRK2 mutations in United States PD cases with a family history of the disease. We have identified two novel mutations in LRRK2.
- Published
- 2007
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