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

Roy N. Alcalay, Helen Mejia-Santana, Ming Xin Tang, Llency 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. CoteSteven J. Frucht, Blair Ford, Michael Rezak, Kevin Novak, Joseph H. Friedman, Ronald Pfeiffer, Laura Marsh, Bradley Hiner, Andrew Siderowf, Elise Caccappolo, Ruth Ottman, Lorraine N. Clark, Karen S. Marder

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1517-1522
Number of pages6
JournalArchives of Neurology
Volume66
Issue number12
DOIs
StatePublished - Dec 1 2009

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Parkinson Disease
Phenotype
Gait
Mutation
Tremor
Demography
Carrier
Parkinson's Disease
Onset
Movement Disorders
Levodopa
Age of Onset
Observational Studies
Cross-Sectional Studies
Logistic Models
Odds Ratio
Outcome Assessment (Health Care)
DNA
Ashkenazi

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Alcalay, R. N., Mejia-Santana, H., Tang, M. X., Rosado, L., Verbitsky, M., Kisselev, S., ... Marder, K. S. (2009). Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease. Archives of Neurology, 66(12), 1517-1522. https://doi.org/10.1001/archneurol.2009.267

Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease. / Alcalay, Roy N.; Mejia-Santana, Helen; Tang, Ming Xin; Rosado, Llency; 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 J.; Ford, Blair; Rezak, Michael; Novak, Kevin; Friedman, Joseph H.; Pfeiffer, Ronald; Marsh, Laura; Hiner, Bradley; Siderowf, Andrew; Caccappolo, Elise; Ottman, Ruth; Clark, Lorraine N.; Marder, Karen S.

In: Archives of Neurology, Vol. 66, No. 12, 01.12.2009, p. 1517-1522.

Research output: Contribution to journalArticle

Alcalay, RN, Mejia-Santana, H, Tang, MX, Rosado, L, Verbitsky, M, Kisselev, S, Ross, BM, Louis, ED, Comella, CL, Colcher, A, Jennings, D, Nance, MA, Bressman, S, Scott, WK, Tanner, C, Mickel, SF, Andrews, HF, Waters, CH, Fahn, S, Cote, LJ, Frucht, SJ, Ford, B, Rezak, M, Novak, K, Friedman, JH, Pfeiffer, R, Marsh, L, Hiner, B, Siderowf, A, Caccappolo, E, Ottman, R, Clark, LN & Marder, KS 2009, 'Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease', Archives of Neurology, vol. 66, no. 12, pp. 1517-1522. https://doi.org/10.1001/archneurol.2009.267
Alcalay RN, Mejia-Santana H, Tang MX, Rosado L, Verbitsky M, Kisselev S et al. Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease. Archives of Neurology. 2009 Dec 1;66(12):1517-1522. https://doi.org/10.1001/archneurol.2009.267
Alcalay, Roy N. ; Mejia-Santana, Helen ; Tang, Ming Xin ; Rosado, Llency ; 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 J. ; Ford, Blair ; Rezak, Michael ; Novak, Kevin ; Friedman, Joseph H. ; Pfeiffer, Ronald ; Marsh, Laura ; Hiner, Bradley ; Siderowf, Andrew ; Caccappolo, Elise ; Ottman, Ruth ; Clark, Lorraine N. ; Marder, Karen S. / Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease. In: Archives of Neurology. 2009 ; Vol. 66, No. 12. pp. 1517-1522.
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title = "Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease",
abstract = "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.",
author = "Alcalay, {Roy N.} and Helen Mejia-Santana and Tang, {Ming Xin} and Llency Rosado and Miguel Verbitsky and Sergey Kisselev and Ross, {Barbara M.} and Louis, {Elan D.} and Comella, {Cynthia L.} and Amy Colcher and Danna Jennings and Nance, {Martha A.} and Susan Bressman and Scott, {William K} and Caroline Tanner and Mickel, {Susan F.} and Andrews, {Howard F.} and Waters, {Cheryl H.} and Stanley Fahn and Cote, {Lucien J.} and Frucht, {Steven J.} and Blair Ford and Michael Rezak and Kevin Novak and Friedman, {Joseph H.} and Ronald Pfeiffer and Laura Marsh and Bradley Hiner and Andrew Siderowf and Elise Caccappolo and Ruth Ottman and Clark, {Lorraine N.} and Marder, {Karen S.}",
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TY - JOUR

T1 - Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease

AU - Alcalay, Roy N.

AU - Mejia-Santana, Helen

AU - Tang, Ming Xin

AU - Rosado, Llency

AU - Verbitsky, Miguel

AU - Kisselev, Sergey

AU - Ross, Barbara M.

AU - Louis, Elan D.

AU - Comella, Cynthia L.

AU - Colcher, Amy

AU - Jennings, Danna

AU - Nance, Martha A.

AU - Bressman, Susan

AU - Scott, William K

AU - Tanner, Caroline

AU - Mickel, Susan F.

AU - Andrews, Howard F.

AU - Waters, Cheryl H.

AU - Fahn, Stanley

AU - Cote, Lucien J.

AU - Frucht, Steven J.

AU - Ford, Blair

AU - Rezak, Michael

AU - Novak, Kevin

AU - Friedman, Joseph H.

AU - Pfeiffer, Ronald

AU - Marsh, Laura

AU - Hiner, Bradley

AU - Siderowf, Andrew

AU - Caccappolo, Elise

AU - Ottman, Ruth

AU - Clark, Lorraine N.

AU - Marder, Karen S.

PY - 2009/12/1

Y1 - 2009/12/1

N2 - 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.

AB - 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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