Marras Connie, Alcalay Roy N, Caspell-Garcia Chelsea, Coffey Christopher, Chan Piu, Duda John E, Facheris Maurizio F, Fernández-Santiago Rubén, Ruíz-Martínez Javier, Mestre Tiago, Saunders-Pullman Rachel, Pont-Sunyer Claustre, Tolosa Eduardo, Waro Bjorg
Toronto Western Hospital Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson's Disease, University of Toronto, Toronto, Ontario, Canada.
Department of Neurology, Columbia University Medical Center, New York, New York, USA.
Mov Disord. 2016 Aug;31(8):1192-202. doi: 10.1002/mds.26614. Epub 2016 Apr 19.
Parkinson's disease (PD) associated with LRRK2 mutations has been described as similar to idiopathic PD with minor clinical differences. No study has compared the clinical features of LRRK2-associated PD due to different mutations. The objective of this study was to compare LRRK2-associated PD due to G2019S and G2385R mutations and to compare each to idiopathic PD.
Sites within the international LRRK2 Cohort Consortium undertook family-based, community-based, or clinic-based studies to gather clinical data on manifesting carriers and patients with idiopathic PD.
Five hundred sixteen PD patients with the G2019S mutation, 199 with the G2385R mutation, and 790 patients with idiopathic PD were included in the data set. Adjusted for age, sex, disease duration, and levodopa-equivalent daily dose, mean MDS-UPDRS part II or III scores and the frequency of motor fluctuations were higher in the G2385R mutation carriers than in either the G2019S mutation carriers or idiopathic PD patients. G2019S mutation carriers had significantly lower UPDRS part III scores than idiopathic PD patients. Both G2019S and G2385R mutation carriers had a higher proportion of the postural instability gait disorder phenotype compared with idiopathic PD patients. LRRK2 G2019S PD patients had better UPSIT scores and lower Geriatric Depression Scale scores than idiopathic PD patients in adjusted analyses.
G2385R and G2019S PD appear to have motor differences that may be explained by contrasting local treatment or measurement practices or differences in the biology of the disease. Longitudinal studies should evaluate whether progression is faster in G2385R mutation carriers compared with G2019S PD or idiopathic PD. © 2016 International Parkinson and Movement Disorder Society.
与亮氨酸丰富重复激酶2（LRRK2）突变相关的帕金森病（PD）被描述为与特发性PD相似，临床差异较小。尚无研究比较因不同突变导致的LRRK2相关PD的临床特征。本研究的目的是比较因G2019S和G2385R突变导致的LRRK2相关PD，并将二者与特发性PD进行比较。
国际LRRK2队列联盟内的研究点开展了基于家系、社区或诊所的研究，以收集症状性携带者和特发性PD患者的临床数据。
数据集纳入了516例携带G2019S突变的PD患者、199例携带G2385R突变的患者和790例特发性PD患者。在对年龄、性别、病程和左旋多巴等效日剂量进行校正后，G2385R突变携带者的平均MDS-UPDRS第二部分或第三部分评分以及运动波动频率高于G2019S突变携带者或特发性PD患者。G2019S突变携带者的UPDRS第三部分评分显著低于特发性PD患者。与特发性PD患者相比，G2019S和G2385R突变携带者中姿势不稳步态障碍表型的比例更高。在校正分析中，LRRK2 G2019S PD患者的UPSIT评分更好，老年抑郁量表评分更低。
G2385R和G2019S PD似乎存在运动差异，这可能是由于局部治疗或测量方法不同或疾病生物学差异所致。纵向研究应评估G2385R突变携带者与G2019S PD或特发性PD相比，疾病进展是否更快。©2016国际帕金森病和运动障碍协会。
