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Vol. 4, No. 5, 2007
Issue release date: July 2007
Section title: Original Paper
Neurodegenerative Dis 2007;4:386–391
(DOI:10.1159/000105160)

Comprehensive Screening of a North American Parkinson’s Disease Cohort for LRRK2 Mutation

Johnson J. · Paisán-Ruíz C. · Lopez G. · Crews C. · Britton A. · Malkani R. · Evans E.W. · McInerney-Leo A. · Jain S. · Nussbaum R.L. · Foote K.D. · Mandel R.J. · Crawley A. · Reimsnider S. · Fernandez H.H. · Okun M.S. · Gwinn-Hardy K. · Singleton A.B.
aLaboratory of Neurogenetics, National Institute on Aging, bNeurogenetics Branch, National Institute of Neurological Disorders and Stroke and cGenetic Diseases Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Md.; dMedical Genetics, University of California, San Francisco, Calif., and eMovement Disorders Center, University of Florida, Gainesville, Fla., USA

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 8/22/2006
Accepted: 11/15/2006
Published online: 7/6/2007

Number of Print Pages: 6
Number of Figures: 3
Number of Tables: 2

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: http://www.karger.com/NDD

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.


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 8/22/2006
Accepted: 11/15/2006
Published online: 7/6/2007

Number of Print Pages: 6
Number of Figures: 3
Number of Tables: 2

ISSN: 1660-2854 (Print)
eISSN: 1660-2862 (Online)

For additional information: http://www.karger.com/NDD


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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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