Miriam Ostrozovicova, Gertrud Tamas, Agsha Atputhavadivel, Petr Dusek, Milan Grofik, Vladimir Han, Petr Holly, Robert Jech, Katarina Kalinova, Peter Klivenyi, Norbert Kovacs, Kristina Kulcsarova, Egon Kurca, Alexandra Lackova, Hamin Lee, Patrick Lewis, Veronika Magocova, Maria Marekova, David Murphy, Ai Nagano, Jan Necpal, David Pinter, Miroslava Rabajdova, Evzen Ruzicka, Tereza Serranova, Katarzyna Smilowska, Krisztina Soos, Igor Straka, Tatiana Svorenova, Peter Valkovic, Katerina Zarubova, Zuzana Gdovinova, Henry Houlden, Mie Rizig, Matej Skorvanek
{"title":"中欧早发性和家族性帕金森病患者LRRK2 p.L1795F变异的患病率和临床特征","authors":"Miriam Ostrozovicova, Gertrud Tamas, Agsha Atputhavadivel, Petr Dusek, Milan Grofik, Vladimir Han, Petr Holly, Robert Jech, Katarina Kalinova, Peter Klivenyi, Norbert Kovacs, Kristina Kulcsarova, Egon Kurca, Alexandra Lackova, Hamin Lee, Patrick Lewis, Veronika Magocova, Maria Marekova, David Murphy, Ai Nagano, Jan Necpal, David Pinter, Miroslava Rabajdova, Evzen Ruzicka, Tereza Serranova, Katarzyna Smilowska, Krisztina Soos, Igor Straka, Tatiana Svorenova, Peter Valkovic, Katerina Zarubova, Zuzana Gdovinova, Henry Houlden, Mie Rizig, Matej Skorvanek","doi":"10.1002/mdc3.70045","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":19029,"journal":{"name":"Movement Disorders Clinical Practice","volume":" ","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Prevalence and Clinical Characteristics of the LRRK2 p.L1795F Variant in Central Europeans with Early-Onset and Familial Parkinson's Disease.\",\"authors\":\"Miriam Ostrozovicova, Gertrud Tamas, Agsha Atputhavadivel, Petr Dusek, Milan Grofik, Vladimir Han, Petr Holly, Robert Jech, Katarina Kalinova, Peter Klivenyi, Norbert Kovacs, Kristina Kulcsarova, Egon Kurca, Alexandra Lackova, Hamin Lee, Patrick Lewis, Veronika Magocova, Maria Marekova, David Murphy, Ai Nagano, Jan Necpal, David Pinter, Miroslava Rabajdova, Evzen Ruzicka, Tereza Serranova, Katarzyna Smilowska, Krisztina Soos, Igor Straka, Tatiana Svorenova, Peter Valkovic, Katerina Zarubova, Zuzana Gdovinova, Henry Houlden, Mie Rizig, Matej Skorvanek\",\"doi\":\"10.1002/mdc3.70045\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":19029,\"journal\":{\"name\":\"Movement Disorders Clinical Practice\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-03-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Movement Disorders Clinical Practice\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/mdc3.70045\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Movement Disorders Clinical Practice","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/mdc3.70045","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Prevalence and Clinical Characteristics of the LRRK2 p.L1795F Variant in Central Europeans with Early-Onset and Familial Parkinson's Disease.
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.
期刊介绍：
Movement Disorders Clinical Practice- is an online-only journal committed to publishing high quality peer reviewed articles related to clinical aspects of movement disorders which broadly include phenomenology (interesting case/case series/rarities), investigative (for e.g- genetics, imaging), translational (phenotype-genotype or other) and treatment aspects (clinical guidelines, diagnostic and treatment algorithms)
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