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This Article Figures Only Full Text Full Text (PDF) CME: Take the course for this article: Volume 70, Number 7, February 12, 2008 All Versions of this Article: 01.WNL.0000280574.17166.26v1 70/7/521    most recent Correspondence: Submit a response Correspondence: View responses Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen-Plotkin, A. S. Articles by Deerlin, V. M. V. Search for Related Content PubMed PubMed Citation Articles by Chen-Plotkin, A. S. Articles by Deerlin, V. M. V. Related Collections Volumetric MRI Parkinson's disease/Parkinsonism Frontotemporal dementia Parkinson's disease with dementia Corticobasal degeneration Dementia aphasia All Genetics

Corticobasal syndrome and primary progressive aphasia as manifestations of LRRK2 gene mutations

From the Center for Neurodegenerative Disease Research, Institute on Aging and Department of Pathology and Laboratory Medicine (A.S.C.-P., W.Y., E.M.W., C.M.C., V.M.-Y.L., J.Q.T., V.M.V.D.), and Department of Neurology (A.S.C.-P., C.A., H.I.H., C.M.C., M.G.), University of Pennsylvania School of Medicine, Philadelphia; and Department of Neurology (B.L.M.), University of California San Francisco.

Address correspondence and reprint requests to Dr. Vivianna Van Deerlin, University of Pennsylvania Health System, Dept. of Pathology and Laboratory Medicine, 3400 Spruce Street, 7.103 Founders Pavilion, Philadelphia, PA 19104 vivianna{at}mail.med.upenn.edu

Background: Mutations in the LRRK2 gene are an important cause of familial and nonfamilial parkinsonism. Despite pleomorphic pathology, LRRK2 mutations are believed to manifest clinically as typical Parkinson disease (PD). However, most genetic screens have been limited to PD clinic populations.

Objective: To clinically characterize LRRK2 mutations in cases recruited from a spectrum of neurodegenerative diseases.

Methods: We screened for the common G2019S mutation and several additional previously reported LRRK2 mutations in 434 individuals. A total of 254 patients recruited from neurodegenerative disease clinics and 180 neurodegenerative disease autopsy cases from the University of Pennsylvania brain bank were evaluated.

Results: Eight cases were found to harbor a LRRK2 mutation. Among patients with a mutation, two presented with cognitive deficits leading to clinical diagnoses of corticobasal syndrome and primary progressive aphasia.

Conclusion: The clinical presentation of LRRK2-associated neurodegenerative disease may be more heterogeneous than previously assumed.

GLOSSARY: AD = Alzheimer disease; ALS = amyotrophic lateral sclerosis; CBD = corticobasal degeneration; CBS = corticobasal syndrome; CDNR = Center for Neurodegenerative Disease Research; DLB = dementia with Lewy bodies; EPS = extrapyramidal symptoms; FTD = frontotemporal dementia; FTLD = frontotemporal lobar degeneration; FWHM = full width at half maximum; LBVAD = Lewy body variant of AD; PD = Parkinson disease; PPA = primary progressive aphasia; PSP = progressive supranuclear palsy; UPenn = University of Pennsylvania; UCSF = University of California San Francisco.

e-Pub ahead of print on October 3, 2007, at www.neurology.org.

Supported by grants from the NIH (P01 AG17586, P01 AG09215, P01 AG11542, P01 AG14382, P01 AG14449, P01 AG19724, P30 AG10124, R01 AG15116, and R01 NS44266). V.M.Y.L. is The John H. Ware, 3rd Professor of AD research. J.Q.T. is the William Maul Measey-Truman G. Schnabel, Jr. Professor of Geriatric Medicine and Gerontology.

Disclosure: The authors report no conflicts of interest.

Received January 22, 2007. Accepted in final form July 13, 2007.

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