Updated MDSGene review on the clinical and genetic spectrum of LRRK2 variants in Parkinson´s disease
Clara Krüger, Shen‐Yang Lim, Alissa Buhrmann, Fenja L. Fahrig, Carolin Gabbert, Natascha Bahr, Harutyun Madoev, Connie Marras, Christine Klein, Katja Lohmann
Abstract
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.