A Possible Modifying Effect of the G2019S Mutation in the LRRK2 Gene on GBA Parkinson's Disease
A Possible Modifying Effect of the G2019S Mutation in the LRRK2 Gene on GBA Parkinson's Disease
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DOI：
10.1002/mds.28066
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发表时间：
2020-04-30
影响因子：
8.6
通讯作者：
Thaler, Avner
中科院分区：
文献类型：
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作者：
Omer, Nurit;Giladi, Nir;Thaler, Avner
背景：LRRK 2-PD患者的帕金森病（PD）表型较轻，GBA-PD患者的PD表型较重;但是，在此情况下，目的本研究的目的是探讨与单基因突变相比，双基因突变PD患者的表型表达，方法对PD患者进行G2019 S-LRRK 2突变和GBA基因中9个突变的基因分型。受试者分为5组：特发性PD、轻度GBA-PD、重度GBA-PD、LRRK 2-PD和LRRK 2 +GBA-PD。结果1090例特发性PD患者，155例LRRK 2-PD患者，155例轻度GBA-PD患者，56例重度GBA-PD患者，27例LRRK 2 +GBA-PD患者参与了本研究。结论LRRK 2 + GBA-PD患者与LRRK 2-PD患者的神经功能相似，LRRK 2在表型上的优势作用大于GBA。(c)2020国际帕金森和运动障碍协会
Background The phenotype of Parkinson's disease (PD) is milder among patients with LRRK2-PD and more severe among patients with GBA-PD; however, whether an additive phenotypical effect occurs among dual-mutation carriers requires validation.Objective The objective of this study was to explore the phenotypic expression of patients with PD who carry mutations in both genes compared with a single-mutation presentation.Methods Patients with PD were genotyped for the G2019S-LRRK2 mutation and 9 mutations in the GBA gene. Subjects were classified into 5 groups: idiopathic PD, mild GBA-PD, severe GBA-PD, LRRK2-PD, and LRRK2+GBA-PD. Clinical symptoms were evaluated using performance-based measures.Results A total of 1090 patients with idiopathic PD, 155 patients with LRRK2-PD, 155 patients with mild GBA-PD, 56 patients with severe GBA-PD, and 27 patients with LRRK2+GBA-PD participated in this study. The patients with LRRK2-PD and LRRK2+GBA-PD exhibited lower scores on total Unified Parkinson's Disease Rating Scale (P < 0.01) and better olfaction (P < 0.01) compared with GBA-PD.Conclusions Patients with LRRK2+GBA-PD were symptomatically similar to patients with LRRK2-PD, suggesting a dominant effect of LRRK2 over GBA in the phenotypic presentation. (c) 2020 International Parkinson and Movement Disorder Society