Alcalay Roy Nissim author Columbia University. Center for Parkinson's Disease and Other Movement Disorders Mejia-Santana Helen author Columbia University. Sergievsky Center Tang Ming Xin author Columbia University. Biostatistics Rosado Llency E. author Columbia University. Sergievsky Center Verbitsky Miguel author Kisselev Sergey author Columbia University. Pathology and Cell Biology Ross Barbara M. author Columbia University. Taub Institute Louis Elan D. author Columbia University. Center for Parkinson's Disease and Other Movement Disorders Columbia University. Epidemiology Comella Cynthia L. author Colcher Amy author Jennings Danna author Nance Martha A. author Bressman Susan author Scott William K. author Tanner Caroline author Mickel Susan F. author Andrews Howard F. author Columbia University. Biostatistics Waters Cheryl H. author Columbia University. Center for Parkinson's Disease and Other Movement Disorders Fahn Stanley author Columbia University. Center for Parkinson's Disease and Other Movement Disorders Cote Lucien J. author Columbia University. Neurology Frucht Steven author Columbia University. Neurology Ford Blair author Columbia University. Center for Parkinson's Disease and Other Movement Disorders Rezak Michael author Novak Kevin author Friedman Joseph H. author Pfeiffer Ronald author Marsh Laura author Hiner Bradley author Siderowf Andrew author Van Vliet Elise A. author Columbia University. Neurology Ottman Ruth author Columbia University. Epidemiology Clark Lorraine N. author Columbia University. Pathology and Cell Biology Marder Karen author Columbia University. Neurology Columbia University. Center for Parkinson's Disease and Other Movement Disorders originator text Articles 2009 manuscript version English Objective: To determine the motor phenotype of LRRK2 G2019S mutation carriers. LRRK2 mutation carriers were previously reported to manifest the tremor dominant motor phenotype, which has been associated with slower motor progression and less cognitive impairment compared with the postural instability and gait difficulty (PIGD) phenotype. Design: Cross-sectional observational study. Setting: Thirteen movement disorders centers. Participants: Nine hundred twenty-five early-onset Parkinson disease cases defined as age at onset younger than 51 years. Main Outcome Measures: LRRK2 mutation status and Parkinson disease motor phenotype: tremor dominant or PIGD. Demographic information, family history of Parkinson disease, and the Unified Parkinson's Disease Rating Scale score were collected on all participants. DNA samples were genotyped for LRRK2 mutations (G2019S, I2020T, R1441C, and Y1699C). Logistic regression was used to examine associations of G2019S mutation status with motor phenotype adjusting for disease duration, Ashkenazi Jewish ancestry, levodopa dose, and family history of Parkinson disease. Results: Thirty-four cases (3.7%) (14 previously reported) were G2019S carriers. No other mutations were found. Carriers were more likely to be Ashkenazi Jewish (55.9% vs 11.9%; P < .001) but did not significantly differ in any other demographic or disease characteristics. Carriers had a lower tremor score (P = .03) and were more likely to have a PIGD phenotype (92.3% vs 58.9%; P = .003). The association of the G2019S mutation with PIGD phenotype remained after controlling for disease duration and Ashkenazi Jewish ancestry (odds ratio, 17.7; P < .001). Conclusion: Early-onset Parkinson disease G2019S LRRK2 carriers are more likely to manifest the PIGD phenotype, which may have implications for disease course. Neurosciences 66 12 1442 1444 2009 0003-9942 http://dx.doi.org/10.1001/archneurol.2009.267 http://hdl.handle.net/10022/AC:P:9929 NNC NNC 2011-03-10 10:01:55 -0500 2012-08-28 16:51:31 -0400 3054 eng