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. 2025 Aug;12(8):1132-1139.
doi: 10.1002/mdc3.70045. Epub 2025 Mar 22.

Prevalence and Clinical Characteristics of the LRRK2 p.L1795F Variant in Central Europeans with Early-Onset and Familial Parkinson's Disease

Miriam Ostrozovicova  1   2   3 , Gertrud Tamas  4 , Agsha Atputhavadivel  3 , Petr Dusek  5 , Milan Grofik  6 , Vladimir Han  1   2 , Petr Holly  5 , Robert Jech  5 , Katarina Kalinova  7 , Peter Klivenyi  8 , Norbert Kovacs  9 , Kristina Kulcsarova  1   2   10 , Egon Kurca  6 , Alexandra Lackova  1   2 , Hamin Lee  3 , Patrick Lewis  11   12 , Veronika Magocova  1   2 , Maria Marekova  13 , David Murphy  14 , Ai Nagano  3 , Jan Necpal  15 , David Pinter  9 , Miroslava Rabajdova  13 , Evzen Ruzicka  5 , Tereza Serranova  5 , Katarzyna Smilowska  16 , Krisztina Soos  4 , Igor Straka  17 , Tatiana Svorenova  1   2 , Peter Valkovic  17   18 , Katerina Zarubova  19 , Zuzana Gdovinova  1   2 , Henry Houlden  3 , Mie Rizig  3 , Matej Skorvanek  1   2 ; CEGEMOD consortium
Collaborators, Affiliations

Prevalence and Clinical Characteristics of the LRRK2 p.L1795F Variant in Central Europeans with Early-Onset and Familial Parkinson's Disease

Miriam Ostrozovicova et al. Mov Disord Clin Pract. 2025 Aug.

Abstract

Background: Leucine-rich repeat kinase 2 (LRRK2) p.L1795F variant was proposed as a genetic risk factor for Parkinson's disease (PD). However, its prevalence, phenotype, and origin remain unknown.

Objective: The aim was to evaluate the frequency and phenotype of p.L1795F in early-onset PD (EOPD) and familial PD compared to healthy controls (HC) in Central Europe.

Methods: Whole-exome sequencing was used to screen 219 EOPD and familial PD patients of Central Europeans compared to HC. Sanger sequencing assessed segregation. Detailed clinical phenotype was evaluated for all positive carriers.

Results: p.L1795F was identified in 1.37% (3/219) and 3.23% of familial cases (3/93), with no carriers among HCs (0/303). Segregation analysis confirmed association with PD. Carriers were traced to the eastern Slovak-Hungarian region. It also appears to be associated with a more aggressive phenotype.

Conclusion: Our data indicate that p.L1795F contributes to PD in Central Europe. Further exploration in larger cohorts is warranted to establish its contribution to global PD risk.

Keywords: L1795F; Parkinson's disease; genetics; leucine‐rich repeat kinase 2 (LRRK2); mutation; risk factor.

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Conflict of interest statement

Ethical Compliance Statement: This study was approved by the University Hospital of L. Pasteur Research Ethics Board. Written informed patient consent was obtained from each participant. We confirm that we have read the journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest: This study was funded by the Slovak Grant and Development Agency under contracts APVV‐22‐0279, by the Slovak Scientific Grant Agency under contract VEGA 1/0712/22, and by the EU Renewal and Resilience Plan “Large Projects for Excellent Researchers” under grant number 09I03‐03‐V03‐00007. The Czech center was supported by project number LX22NPO5107 (MEYS): financed by the European Union–Next Generation EU and by the Czech Health Research Council grant NU21‐04‐00535 and MH CZ‐DRO‐VFN64165. P.K. is supported by a TKP2021‐EGA‐32 grant that has been implemented with the support provided by the Ministry of Culture and Innovation of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021‐EGA funding scheme. P.K.'s work also contributed to the Rare Neurological Disorders‐European Reference Network. P.L. is a Royal Society Industry Research Fellow (IF\R2\222002). The authors declare that there are no conflicts of interest relevant to this work.

Financial Disclosures for the Previous 12 Months: The authors declare that there are no additional disclosures to report.

Figures

FIG. 1
FIG. 1
Pedigrees of LRRK2 (leucine‐rich repeat kinase 2) p.L1795F‐positive PD patients. AAO, age at onset; CP, cerebral palsy; G/G, homozygous for the wild‐type G allele; G/T, heterozygous p.L1795F variant carrier; y, years.
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Update of

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