Ostrozovicova Miriam, Tamas Gertrud, Atputhavadivel Agsha, Dusek Petr, Grofik Milan, Han Vladimir, Holly Petr, Jech Robert, Kalinova Katarina, Klivenyi Peter, Kovacs Norbert, Kulcsarova Kristina, Kurca Egon, Lackova Alexandra, Lee Hamin, Lewis Patrick, Magocova Veronika, Marekova Maria, Murphy David, Nagano Ai, Necpal Jan, Pinter David, Rabajdova Miroslava, Ruzicka Evzen, Serranova Tereza, Smilowska Katarzyna, Soos Krisztina, Straka Igor, Svorenova Tatiana, Valkovic Peter, Zarubova Katerina, Gdovinova Zuzana, Houlden Henry, Rizig Mie, Skorvanek Matej
Department of Neurology, P.J. Safarik University, Kosice, Slovak Republic.
Department of Neurology, University Hospital of L. Pasteur, Kosice, Slovak Republic.
Mov Disord Clin Pract. 2025 Mar 22. doi: 10.1002/mdc3.70045.
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.
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.
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.
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.
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.
富含亮氨酸重复激酶2（LRRK2）p.L1795F变异被认为是帕金森病（PD）的一个遗传风险因素。然而，其患病率、表型及起源仍不清楚。
旨在评估中欧早发性帕金森病（EOPD）和家族性帕金森病中p.L1795F相对于健康对照（HC）的频率和表型。
采用全外显子组测序对219例中欧EOPD和家族性帕金森病患者与健康对照进行筛查。桑格测序评估分离情况。对所有阳性携带者评估详细的临床表型。
在1.37%（3/219）的病例及3.23%的家族性病例（3/93）中鉴定出p.L1795F，健康对照中无携带者（0/303）。分离分析证实其与帕金森病相关。携带者追溯至斯洛伐克东部-匈牙利地区。它似乎也与更具侵袭性的表型相关。
我们的数据表明p.L1795F在中欧对帕金森病有影响。有必要在更大队列中进一步探索以确定其对全球帕金森病风险的影响。
