Abstract：
BACKGROUND: Variants in the GBA1 gene cause the lysosomal storage disorder Gaucher disease (GD). They are also risk factors for Parkinson\'s disease (PD), and modify the expression of the PD phenotype. The penetrance of GBA1 variants in PD is incomplete, and the ability to determine who among GBA1 variant carriers are at higher risk of developing PD, would represent an advantage for prognostic and trial design purposes.
OBJECTIVE: To compare the motor and non-motor phenotype of GBA1 carriers and non-carriers.
METHODS: We present the cross-sectional results of the baseline assessment from the RAPSODI study, an online assessment tool for PD patients and GBA1 variant carriers. The assessment includes clinically validated questionnaires, a tap-test, the University of Pennsyllvania Smell Identification Test and cognitive tests. Additional, homogeneous data from the PREDICT-PD cohort were included.
RESULTS: A total of 379 participants completed all parts of the RAPSODI assessment (89 GBA1-negative controls, 169 GBA1-negative PD, 47 GBA1-positive PD, 47 non-affected GBA1 carriers, 27 GD). Eighty-six participants were recruited through PREDICT-PD (43 non-affected GBA1 carriers and 43 GBA1-negative controls). GBA1-positive PD patients showed worse performance in visual cognitive tasks and olfaction compared to GBA1-negative PD patients. No differences were detected between non-affected GBA1 carriers carriers and GBA1-negative controls. No phenotypic differences were observed between any of the non-PD groups.
CONCLUSIONS: Our results support previous evidence that GBA1-positive PD has a specific phenotype with more severe non-motor symptoms. However, we did not reproduce previous findings of more frequent prodromal PD signs in non-affected GBA1 carriers.
OBJECTIVE: To compare the motor and non-motor phenotype of GBA1 carriers and non-carriers.
METHODS: We present the cross-sectional results of the baseline assessment from the RAPSODI study, an online assessment tool for PD patients and GBA1 variant carriers. The assessment includes clinically validated questionnaires, a tap-test, the University of Pennsyllvania Smell Identification Test and cognitive tests. Additional, homogeneous data from the PREDICT-PD cohort were included.
RESULTS: A total of 379 participants completed all parts of the RAPSODI assessment (89 GBA1-negative controls, 169 GBA1-negative PD, 47 GBA1-positive PD, 47 non-affected GBA1 carriers, 27 GD). Eighty-six participants were recruited through PREDICT-PD (43 non-affected GBA1 carriers and 43 GBA1-negative controls). GBA1-positive PD patients showed worse performance in visual cognitive tasks and olfaction compared to GBA1-negative PD patients. No differences were detected between non-affected GBA1 carriers carriers and GBA1-negative controls. No phenotypic differences were observed between any of the non-PD groups.
CONCLUSIONS: Our results support previous evidence that GBA1-positive PD has a specific phenotype with more severe non-motor symptoms. However, we did not reproduce previous findings of more frequent prodromal PD signs in non-affected GBA1 carriers.
摘要：
背景：GBA1基因变异体可导致溶酶体贮积症戈谢病（GD）。它们也是帕金森病（PD）的危险因素，并修饰PD表型的表达。PD中GBA1变体的外显率不完整,以及确定GBA1变异携带者中谁患PD的风险较高的能力，将代表预后和试验设计目的的优势。
目的：比较GBA1携带者和非携带者的运动和非运动表型。
方法：我们提供了来自RAPSODI研究的基线评估的横截面结果，PD患者和GBA1变异携带者的在线评估工具。评估包括临床验证的问卷，点击测试，Pennsylvania大学气味识别测试和认知测试。额外,纳入了PREDICT-PD队列的同质数据.
结果：共有379名参与者完成了RAPSODI评估的所有部分（89个GBA1阴性对照，169GBA1-阴性PD，47GBA1阳性PD，47个不受影响的GBA1运营商，27GD）。通过PREDICT-PD招募了86名参与者（43名未受影响的GBA1携带者和43名GBA1阴性对照）。与GBA1阴性PD患者相比，GBA1阳性PD患者在视觉认知任务和嗅觉方面表现较差。在未受影响的GBA1携带者和GBA1阴性对照之间没有检测到差异。在任何非PD组之间没有观察到表型差异。
结论：我们的结果支持先前的证据，即GBA1阳性PD具有更严重的非运动症状的特定表型。然而,我们没有重现之前在未受影响的GBA1携带者中更频繁的前驱PD征象的发现.
目的：比较GBA1携带者和非携带者的运动和非运动表型。
方法：我们提供了来自RAPSODI研究的基线评估的横截面结果，PD患者和GBA1变异携带者的在线评估工具。评估包括临床验证的问卷，点击测试，Pennsylvania大学气味识别测试和认知测试。额外,纳入了PREDICT-PD队列的同质数据.
结果：共有379名参与者完成了RAPSODI评估的所有部分（89个GBA1阴性对照，169GBA1-阴性PD，47GBA1阳性PD，47个不受影响的GBA1运营商，27GD）。通过PREDICT-PD招募了86名参与者（43名未受影响的GBA1携带者和43名GBA1阴性对照）。与GBA1阴性PD患者相比，GBA1阳性PD患者在视觉认知任务和嗅觉方面表现较差。在未受影响的GBA1携带者和GBA1阴性对照之间没有检测到差异。在任何非PD组之间没有观察到表型差异。
结论：我们的结果支持先前的证据，即GBA1阳性PD具有更严重的非运动症状的特定表型。然而,我们没有重现之前在未受影响的GBA1携带者中更频繁的前驱PD征象的发现.
