Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease

Roy Nissim Alcalay; Helen Mejia-Santana; Ming Xin Tang; Llency E. Rosado; Miguel Verbitsky; Sergey Kisselev; Barbara M. Ross; Elan D. Louis; Cynthia L. Comella; Amy Colcher; Danna Jennings; Martha A. Nance; Susan Bressman; William K. Scott; Caroline Tanner; Susan F. Mickel; Howard F. Andrews; Cheryl H. Waters; Stanley Fahn; Lucien J. Cote; Steven Frucht; Blair Ford; Michael Rezak; Kevin Novak; Joseph H. Friedman; Ronald Pfeiffer; Laura Marsh; Bradley Hiner; Andrew Siderowf; Elise A. Van Vliet; Ruth Ottman; Lorraine N. Clark; Karen Marder

Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease
Alcalay, Roy Nissim
Mejia-Santana, Helen
Tang, Ming Xin
Rosado, Llency E.
Verbitsky, Miguel
Kisselev, Sergey
Ross, Barbara M.
Louis, Elan D.
Comella, Cynthia L.
Colcher, Amy
Jennings, Danna
Nance, Martha A.
Bressman, Susan
Scott, William K.
Tanner, Caroline
Mickel, Susan F.
Andrews, Howard F.
Waters, Cheryl H.
Fahn, Stanley
Cote, Lucien J.
Frucht, Steven
Ford, Blair
Rezak, Michael
Novak, Kevin
Friedman, Joseph H.
Pfeiffer, Ronald
Marsh, Laura
Hiner, Bradley
Siderowf, Andrew
Van Vliet, Elise A.
Ottman, Ruth
Clark, Lorraine N.
Marder, Karen
Center for Parkinson's Disease and Other Movement Disorders
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Archives of Neurology
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.
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Roy Nissim Alcalay, Helen Mejia-Santana, Ming Xin Tang, Llency E. Rosado, Miguel Verbitsky, Sergey Kisselev, Barbara M. Ross, Elan D. Louis, Cynthia L. Comella, Amy Colcher, Danna Jennings, Martha A. Nance, Susan Bressman, William K. Scott, Caroline Tanner, Susan F. Mickel, Howard F. Andrews, Cheryl H. Waters, Stanley Fahn, Lucien J. Cote, Steven Frucht, Blair Ford, Michael Rezak, Kevin Novak, Joseph H. Friedman, Ronald Pfeiffer, Laura Marsh, Bradley Hiner, Andrew Siderowf, Elise A. Van Vliet, Ruth Ottman, Lorraine N. Clark, Karen Marder, , Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease, Columbia University Academic Commons, .

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