Background Pathogenic variants in the LRRK2 gene are among the most common genetic causes of autosomal dominant Parkinson’s disease (PD). A recent study provided strong genetic and functional evidence supporting the pathogenicity of the rare missense variant p.L1795F (c.5385G > T), identified exclusively in individuals of European ancestry. However, its prevalence in Southern European populations remains unknown. Objective The aim of the study was to evaluate the frequency of the p.L1795F variant in a cohort of PD patients from Southern Italy. Methods We screened 300 unrelated PD patients using Sanger sequencing to detect the presence of the p.L1795F (c.5385G > T) variant in the LRRK2 gene. Results No carriers of the p.L1795F variant were identified in our Southern Italian cohort. Conclusion These findings suggest that the p.L1795F variant may have very low or undetectable frequency in the Southern Italian population. Our results highlight the importance of including underrepresented geographic regions in genetic screening efforts for PD to better understand the population-specific distribution of pathogenic variants.
No evidence for the LRRK2 p.L1795F variant in a Southern Italian cohort with Parkinson’s disease
Gagliardi M.;Procopio R.
;Felicetti A.;Quattrone A.;Arabia G.;Morelli M.;Gambardella A.;Annesi G.;Quattrone A.
2026-01-01
Abstract
Background Pathogenic variants in the LRRK2 gene are among the most common genetic causes of autosomal dominant Parkinson’s disease (PD). A recent study provided strong genetic and functional evidence supporting the pathogenicity of the rare missense variant p.L1795F (c.5385G > T), identified exclusively in individuals of European ancestry. However, its prevalence in Southern European populations remains unknown. Objective The aim of the study was to evaluate the frequency of the p.L1795F variant in a cohort of PD patients from Southern Italy. Methods We screened 300 unrelated PD patients using Sanger sequencing to detect the presence of the p.L1795F (c.5385G > T) variant in the LRRK2 gene. Results No carriers of the p.L1795F variant were identified in our Southern Italian cohort. Conclusion These findings suggest that the p.L1795F variant may have very low or undetectable frequency in the Southern Italian population. Our results highlight the importance of including underrepresented geographic regions in genetic screening efforts for PD to better understand the population-specific distribution of pathogenic variants.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
