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Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease.
Arch Neurol. 2009 Dec; 66(12):1517-22.AN

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.

Authors+Show Affiliations

Department of Neurology, Columbia University, New York, NY 10032, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20008657

Citation

Alcalay, Roy N., et al. "Motor Phenotype of LRRK2 G2019S Carriers in Early-onset Parkinson Disease." Archives of Neurology, vol. 66, no. 12, 2009, pp. 1517-22.
Alcalay RN, Mejia-Santana H, Tang MX, et al. Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease. Arch Neurol. 2009;66(12):1517-22.
Alcalay, R. N., Mejia-Santana, H., Tang, M. X., Rosado, L., Verbitsky, M., Kisselev, S., Ross, B. M., Louis, E. D., Comella, C. L., Colcher, A., Jennings, D., Nance, M. A., Bressman, S., Scott, W. K., Tanner, C., Mickel, S. F., Andrews, H. F., Waters, C. H., Fahn, S., ... Marder, K. S. (2009). Motor phenotype of LRRK2 G2019S carriers in early-onset Parkinson disease. Archives of Neurology, 66(12), 1517-22. https://doi.org/10.1001/archneurol.2009.267
Alcalay RN, et al. Motor Phenotype of LRRK2 G2019S Carriers in Early-onset Parkinson Disease. Arch Neurol. 2009;66(12):1517-22. PubMed PMID: 20008657.
* Article titles in AMA citation format should be in sentence-case
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 - 2009/12/17/entrez PY - 2009/12/17/pubmed PY - 2010/1/13/medline SP - 1517 EP - 22 JF - Archives of neurology JO - Arch Neurol VL - 66 IS - 12 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. SN - 1538-3687 UR - https://www.unboundmedicine.com/medline/citation/20008657/Motor_phenotype_of_LRRK2_G2019S_carriers_in_early_onset_Parkinson_disease_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/archneurol.2009.267 DB - PRIME DP - Unbound Medicine ER -