학술논문
Comprehensive Screening of a North American Parkinson’s Disease Cohort for LRRK2 Mutation.
Document Type
Article
Author
Johnson, Janel; Paisán-Ruíz, Coro; Lopez, Grisel; Crews, Cynthia; Britton, Angela; Malkani, Roniel; Evans, E.Whitney; McInerney-Leo, Aideen; Jain, Shushant; Nussbaum, Robert L.; Foote, Kelly D.; Mandel, Ronald J.; Crawley, Anthony; Reimsnider, Sharon; Fernandez, Hubert H.; Okun, Michael S.; Gwinn-Hardy, Katrina; Singleton, Andrew B.
Source
Subject
*PARKINSON'S disease
*COHORT analysis
*GENETIC mutation
*PROTEINS
*NORTH Americans
*GENEALOGY
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Language
ISSN
1660-2854
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. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]