Department of Neurology, Sourasky Medical Center, Tel-Aviv, Israel.
J Neural Transm (Vienna). 2009 Nov;116(11):1473-82. doi: 10.1007/s00702-009-0303-0.
Mutations in the leucine rich repeat kinase 2 gene (LRRK2) are recognized as the most common cause of genetic Parkinsonism to date. The G2019S mutation has been implicated as an important determinant of Parkinson's disease (PD) in both Ashkenazi Jewish and North African Arab populations with carrier frequency of 29.7% among familial and 6% in sporadic Ashkenazi Jewish PD cases. PD patients with the G2019S mutation display similar clinical characteristics to patients with sporadic PD. While the function of the LRRK2 protein has yet to be fully determined, its distribution coincides with brain areas most affected by PD. The G2019S mutation is believed to be responsible for up-regulation of LRRK2 kinase activity, which may ultimately play a role in neuronal loss. The utility of LRRK2 G2019S screening in family members of Ashkenazi PD patients is discussed. LRRK2 G2019S mutation carriers without PD may be an ideal population for the study of possible neuroprotective strategies as they become available, and for furthering the understanding of the pathogenesis and long-term clinical outcomes of the disease.
LRRK2 基因（LRRK2）中的突变被认为是迄今为止最常见的遗传帕金森病的原因。G2019S 突变已被认为是阿什肯纳兹犹太人和北非阿拉伯人群中帕金森病（PD）的重要决定因素，在家族性病例中携带者频率为 29.7%，散发性阿什肯纳兹犹太 PD 病例中为 6%。携带 G2019S 突变的 PD 患者表现出与散发性 PD 患者相似的临床特征。虽然 LRRK2 蛋白的功能尚未完全确定，但它的分布与受 PD 影响最严重的大脑区域相吻合。据信，G2019S 突变导致 LRRK2 激酶活性的上调，这可能最终在神经元丧失中起作用。讨论了在阿什肯纳兹 PD 患者的家族成员中进行 LRRK2 G2019S 筛查的实用性。没有 PD 的 LRRK2 G2019S 突变携带者可能是研究可能的神经保护策略的理想人群，因为这些策略会随着时间的推移而出现，并进一步了解疾病的发病机制和长期临床结局。
