Background:Observational studies in Parkinson’s disease (PD) have focused on relatively small numbers of research participants who are studied extensively. The Molecular Integration in Neurological Diagnosis Initiative at the University of Pennsylvania aims to characterize molecular and clinical features of PD in every patient in a large academic center. Objective:To determine the feasibility and interest in a global-capture biomarker research protocol. Additionally, to describe the clinical characteristics and GBA and LRRK2 variant carrier status among participants. Methods:All patients at UPenn with a clinical diagnosis of PD were eligible. Informed consent included options for access to the medical record, future recontact, and use of biosamples for additional studies. A blood sample and a completed questionnaire were obtained from participants. Targeted genotyping for four GBA and eight LRRK2 variants was performed, with plasma and DNA banked for future research. Results:Between September 2018 and December 2019, 704 PD patients were approached for enrollment; 652 (92.6%) enrolled, 28 (3.97%) declined, and 24 (3.41%) did not meet eligibility criteria. Median age was 69 (IQR 63_75) years, disease duration was 5.41 (IQR 2.49_9.95) years, and 11.10%of the cohort was non-white. Disease risk-associated variants in GBA were identified in 39 participants (5.98%) and in LRRK2 in 16 participants (2.45%). Conclusions:We report the clinical and genetic characteristics of PD patients in an all-comers, global capture protocol from an academic center. Patient interest in participation and yield for identification of GBA and LRRK2 mutation carriers is high, demonstrating feasibility of PD clinic-wide molecular characterization.

中文翻译：

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帕金森病的整个临床研究入组：神经诊断中的分子整合 (MIND) 研究

背景：帕金森病 (PD) 的观察性研究主要针对相对较少的研究参与者，但研究参与者却得到了广泛的研究。宾夕法尼亚大学神经学诊断分子整合计划旨在表征大型学术中心每位患者的 PD 分子和临床特征。目的：确定全球捕获生物标志物研究方案的可行性和兴趣。此外，描述参与者的临床特征以及 GBA 和 LRRK2 变异携带者状态。方法：宾夕法尼亚大学所有临床诊断为 PD 的患者均符合资格。知情同意包括获取医疗记录、未来重新联系以及使用生物样本进行其他研究的选项。从参与者那里获取了血液样本和完整的调查问卷。对 4 个 GBA 和 8 个 LRRK2 变体进行了靶向基因分型，并储存了血浆和 DNA 以供未来研究。结果：2018年9月至2019年12月期间，共招募704名PD患者；652 人（92.6%）报名，28 人（3.97%）拒绝，24 人（3.41%）不符合资格标准。中位年龄为 69 (IQR 63_75) 岁，疾病持续时间为 5.41 (IQR 2.49_9.95) 年，队列中 11.10% 为非白人。在 39 名参与者 (5.98%) 中发现了 GBA 疾病风险相关变异，在 16 名参与者 (2.45%) 中发现了 LRRK2 疾病风险相关变异。结论：我们通过学术中心的全球捕获方案报告了 PD 患者的临床和遗传特征。患者对参与 GBA 和 LRRK2 突变携带者鉴定的兴趣很高，这证明了 PD 临床范围分子表征的可行性。