Updated MDSGene review on the clinical and genetic spectrum of LRRK2 variants in Parkinsons disease

Document Type

Article

Publication Date

2-1-2025

Abstract

Pathogenic variants in the LRRK2 gene are one of the most commonly identifiable monogenic causes of Parkinsons 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.

Divisions

fac_med,medicinedept

Funders

International Parkinson and Movement Disorder Society (Movement Disorder Society),International Parkinson and Movement Disorder Society,Parkinsons Foundation,University of Luebeck,Michael J Fox Foundation

Publication Title

NPJ Parkinson's Disease

Volume

11

Issue

1

Publisher

Nature Portfolio

Publisher Location

HEIDELBERGER PLATZ 3, BERLIN, 14197, GERMANY

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