Genome Sequencing in the Parkinson Disease Clinic.
Genome Sequencing in the Parkinson Disease Clinic.
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DOI：
10.1212/nxg.0000000000200002
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发表时间：
2022-08
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遗传变异影响帕金森病（PD）的风险和表现。尽管遗传信息对患者和临床医生具有潜在的兴趣，但在常规PD临床护理中很少进行基因检测。本研究的目的是检查PD患者对综合基因检测的兴趣，并记录2个学术运动障碍诊所对基因组测序可能发现的反应。203名PD患者（年龄63岁，67%为男性）进行了基因组测序，并使用定制面板进行筛选，包括49个与PD、帕金森病或相关疾病相关的基因，以及90个变体PD遗传风险评分。根据研究结果，231名患者（年龄67岁，63%为男性）接受了基因检测的兴趣和对以下内容的反应调查：(1)PD家族风险（LRRK2）；(2) PD痴呆风险（GBA）；(3)帕金森病遗传风险评分；(4)继发性、医学上可操作的变异（BRCA1）。基因组测序显示3%的临床样本中存在LRRK2变异，10%的临床样本中存在GBA风险变异。遗传风险评分呈正态分布，确定41例PD高危人群。在2名受试者（1%）中发现了医学上可采取行动的结果。在我们的调查中，大多数人（82%）回答说他们会与亲戚共享LRRK2变体。当面对痴呆的潜在风险或医学上可操作的发现时，大多数人对检测的兴趣保持不变或增加，大多数（75%）表示有兴趣了解他们的PD遗传风险评分。我们的研究结果强调了对帕金森病患者进行全面基因检测的广泛兴趣，并可能促进基因组测序在临床实践中的整合。
Genetic variants affect both Parkinson disease (PD) risk and manifestations. Although genetic information is of potential interest to patients and clinicians, genetic testing is rarely performed during routine PD clinical care. The goal of this study was to examine interest in comprehensive genetic testing among patients with PD and document reactions to possible findings from genome sequencing in 2 academic movement disorder clinics. In 203 subjects with PD (age = 63 years, 67% male), genome sequencing was performed and filtered using a custom panel, including 49 genes associated with PD, parkinsonism, or related disorders, as well as a 90-variant PD genetic risk score. Based on the results, 231 patients (age = 67 years, 63% male) were surveyed on interest in genetic testing and responses to vignettes covering (1) familial risk of PD (LRRK2); (2) risk of PD dementia (GBA); (3) PD genetic risk score; and (4) secondary, medically actionable variants (BRCA1). Genome sequencing revealed a LRRK2 variant in 3% and a GBA risk variant in 10% of our clinical sample. The genetic risk score was normally distributed, identifying 41 subjects with a high risk of PD. Medically actionable findings were discovered in 2 subjects (1%). In our survey, the majority (82%) responded that they would share a LRRK2 variant with relatives. Most registered unchanged or increased interest in testing when confronted with a potential risk for dementia or medically actionable findings, and most (75%) expressed interest in learning their PD genetic risk score. Our results highlight broad interest in comprehensive genetic testing among patients with PD and may facilitate integration of genome sequencing in clinical practice.