Krüger Clara, Lim Shen-Yang, Buhrmann Alissa, Fahrig Fenja L, Gabbert Carolin, Bahr Natascha, Madoev Harutyun, Marras Connie, Klein Christine, Lohmann Katja
Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
NPJ Parkinsons Dis. 2025 Feb 17;11(1):30. doi: 10.1038/s41531-025-00881-9.
Pathogenic variants in the LRRK2 gene are one of the most commonly identifiable monogenic causes of Parkinson´s disease (PD, PARK-LRRK2). This systematic MDSGene literature review comprehensively summarizes published demographic, clinical, and genetic findings related to LRRK2 variants ( https://www.mdsgene.org/ ). Data on 4660 individuals with 283 different variants were curated. The median age at onset in the PD patients with available information was 56 years, notably, with approximately one-third having PD onset <50 years. Tremor was the most frequently reported initial symptom and more common than reported in other dominantly inherited forms of PD. Of the 211 potentially PD-causing variants, 25 were classified as pathogenic or likely pathogenic, and the remaining 186 (88.2%) were variants of uncertain significance. p.G2019S was the most frequently reported pathogenic variant, followed by p.R1441G and p.R1441C. This systematic review represents the most extensive database on PARK-LRRK2 to date and provides a vital resource to improve precision medicine.
亮氨酸富集重复激酶2（LRRK2）基因的致病性变异是帕金森病（PD，PARK-LRRK2）最常见的可识别单基因病因之一。这项系统的MDSGene文献综述全面总结了已发表的与LRRK2变异相关的人口统计学、临床和遗传学研究结果（https://www.mdsgene.org/）。整理了4660名携带283种不同变异个体的数据。有可用信息的PD患者的发病年龄中位数为56岁，值得注意的是，约三分之一的患者在50岁之前发病。震颤是最常报告的初始症状，比其他显性遗传形式的PD更常见。在211种可能导致PD的变异中，25种被分类为致病性或可能致病性，其余186种（88.2%）为意义未明的变异。p.G2019S是最常报告的致病性变异，其次是p.R1441G和p.R1441C。这项系统综述是迄今为止关于PARK-LRRK2最广泛的数据库，为改善精准医学提供了重要资源。
