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
Department of Neurology, Columbia University, New York, NY 10032, USA.
Arch Neurol. 2009 Dec;66(12):1517-22. doi: 10.1001/archneurol.2009.267.
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.
Cross-sectional observational study.
Thirteen movement disorders centers.
Nine hundred twenty-five early-onset Parkinson disease cases defined as age at onset younger than 51 years.
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.
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).
Early-onset Parkinson disease G2019S LRRK2 carriers are more likely to manifest the PIGD phenotype, which may have implications for disease course.
确定LRRK2基因G2019S突变携带者的运动表型。先前有报道称，LRRK2突变携带者表现为震颤为主的运动表型，与姿势不稳和步态障碍（PIGD）表型相比，其运动进展较慢且认知障碍较少。
横断面观察性研究。
13个运动障碍中心。
925例早发性帕金森病病例，定义为发病年龄小于51岁。
LRRK2突变状态和帕金森病运动表型：震颤为主型或PIGD型。收集所有参与者的人口统计学信息、帕金森病家族史以及统一帕金森病评定量表评分。对DNA样本进行LRRK2突变（G2019S、I2020T、R1441C和Y1699C）基因分型。采用逻辑回归分析，在调整病程、阿什肯纳兹犹太血统、左旋多巴剂量和帕金森病家族史后，研究G2019S突变状态与运动表型之间的关联。
34例（3.7%）（其中14例先前已报道）为G2019S携带者。未发现其他突变。携带者更有可能是阿什肯纳兹犹太人（55.9%对11.9%；P < 0.001），但在其他任何人口统计学或疾病特征方面无显著差异。携带者的震颤评分较低（P = 0.03），且更有可能具有PIGD表型（92.3%对58.9%；P = 0.003）。在控制病程和阿什肯纳兹犹太血统后，G2019S突变与PIGD表型之间的关联仍然存在（优势比为17.7；P < 0.001）。
早发性帕金森病LRRK2基因G2019S突变携带者更有可能表现出PIGD表型，这可能对疾病进程有影响。
