Movement Disorders Unit, Neurological Institute, Tel-Aviv Medical Center, Tel-Aviv, Israel.
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Mov Disord. 2020 Jul;35(7):1249-1253. doi: 10.1002/mds.28066. Epub 2020 Apr 30.
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.
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.
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.
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.
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. © 2020 International Parkinson and Movement Disorder Society.
LRRK2-PD 患者的帕金森病（PD）表型较轻，GBA-PD 患者的表型则更严重；然而，双重突变携带者是否存在累加表型效应尚待验证。
本研究旨在探讨同时携带两种基因突变的 PD 患者的表型表达与单一突变表现的差异。
对 G2019S-LRRK2 突变和 GBA 基因中的 9 个突变进行基因分型。根据基因分型将患者分为 5 组：特发性 PD、轻度 GBA-PD、重度 GBA-PD、LRRK2-PD 和 LRRK2+GBA-PD。采用基于表现的测量方法评估临床症状。
共有 1090 例特发性 PD 患者、155 例 LRRK2-PD 患者、155 例轻度 GBA-PD 患者、56 例重度 GBA-PD 患者和 27 例 LRRK2+GBA-PD 患者参与了本研究。LRRK2-PD 和 LRRK2+GBA-PD 患者的总统一帕金森病评定量表（UPDRS）评分较低（P＜0.01），嗅觉功能较好（P＜0.01），与 GBA-PD 患者相比。
LRRK2+GBA-PD 患者的症状与 LRRK2-PD 患者相似，提示 LRRK2 在表型表现中对 GBA 具有显性作用。© 2020 国际帕金森病和运动障碍学会。
