Gaucher Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel.
Braun School of Public Health and Community Medicine, Hebrew University of Jerusalem, Jerusalem 9124001, Israel.
Int J Mol Sci. 2022 Oct 13;23(20):12211. doi: 10.3390/ijms232012211.
Carriers of GBA1 gene variants have a significant risk of developing Parkinson’s disease (PD). A cohort study of GBA carriers between 40−75 years of age was initiated to study the presence of prodromal PD features. Participants underwent non-invasive tests to assess different domains of PD. Ninety-eight unrelated GBA carriers were enrolled (43 males) at a median age (range) of 51 (40−74) years; 71 carried the N370S variant (c.1226A > G) and 25 had a positive family history of PD. The Montreal Cognitive Assessment (MoCA) was the most frequently abnormal (23.7%, 95% CI 15.7−33.4%), followed by the ultrasound hyperechogenicity (22%, 95% CI 14−32%), Unified Parkinson’s Disease Rating Scale part III (UPDRS-III) (17.2%, 95% CI 10.2−26.4%), smell assessment (12.4%, 95% CI 6.6−20.6%) and abnormalities in sleep questionnaires (11%, 95% CI 5.7−19.4%). Significant correlations were found between tests from different domains. To define the risk for PD, we assessed the bottom 10th percentile of each prodromal test, defining this level as “abnormal”. Then we calculated the percentage of “abnormal” tests for each subject; the median (range) was 4.55 (0−43.5%). Twenty-two subjects had more than 15% “abnormal” tests. The limitations of the study included ascertainment bias of individuals with GBA-related PD in relatives, some incomplete data due to technical issues, and a lack of well-characterized normal value ranges in some tests. We plan to enroll additional participants and conduct longitudinal follow-up assessments to build a model for identifying individuals at risk for PD and investigate interventions aiming to delay the onset or perhaps to prevent full-blown PD.
载脂蛋白 G1 基因变异的携带者患帕金森病 (PD) 的风险显著增加。本研究开展了一项队列研究,纳入 40-75 岁的载脂蛋白 G1 携带者,旨在研究前驱期 PD 特征的存在。参与者接受了非侵入性测试,以评估 PD 的不同领域。共纳入 98 名无血缘关系的载脂蛋白 G1 携带者(43 名男性),中位年龄(范围)为 51(40-74)岁;71 名携带者携带 N370S 变异(c.1226A > G),25 名携带者有 PD 阳性家族史。蒙特利尔认知评估(MoCA)最常异常(23.7%,95%CI 15.7-33.4%),其次是超声回声增强(22%,95%CI 14-32%)、统一帕金森病评定量表第三部分(UPDRS-III)(17.2%,95%CI 10.2-26.4%)、嗅觉评估(12.4%,95%CI 6.6-20.6%)和睡眠问卷异常(11%,95%CI 5.7-19.4%)。不同领域的测试之间存在显著相关性。为了确定 PD 的风险,我们评估了每个前驱性测试的第 10 个百分位数,将该水平定义为“异常”。然后我们计算了每个受试者的“异常”测试百分比;中位数(范围)为 4.55(0-43.5%)。22 名受试者有超过 15%的“异常”测试。该研究的局限性包括亲属中与 GBA 相关 PD 个体的确定偏倚、由于技术问题导致的一些数据不完整,以及一些测试缺乏特征明确的正常范围值。我们计划招募更多参与者并进行纵向随访评估,以建立一种识别 PD 风险个体的模型,并研究旨在延迟发病或预防完全 PD 的干预措施。