Analysis of the genetic variability in Parkinson’s disease from Southern Spain Bandrés Ciga, Sara Mencacci, Niccolò Emmanuele Durán Ogalla, Raquel Barrero Hernández, Francisco Javier Escamilla Sevilla, Francisco Morgan, Sarah Hehir, Jason Vives Montero, Francisco Hardy, John Pittman, Alan M. Parkinson’s disease Genetics Mutations Southern Spain population Next-generation sequencing This work was supported financially by a Medical Research Council and/or Welcome Trust Strategic Award (WT089698/Z/09/Z) and a grant of the Junta de Andalucía to the CTS-438 group. Bandrés Ciga Sara held an FPU fellowship from the Spanish Ministry of Education and Science financed jointly with a short-term stay grant by CEI-Biotic and University of Granada. To date, a large spectrum of genetic variants has been related to familial and sporadic Parkinson's disease (PD) in diverse populations worldwide. However, very little is known about the genetic landscape of PD in Southern Spain, despite its particular genetic landscape coming from multiple historical migrations. We included 134 PD patients in this study, of which 97 individuals were diagnosed with late-onset sporadic PD (LOPD), 28 with early-onset sporadic PD (EOPD), and 9 with familial PD (FPD). Genetic analysis was performed through a next-generation sequencing panel to screen 8 PD-related genes (LRRK2, SNCA, PARKIN, PINK1, DJ-1, VPS35, GBA, and GCH1) in EOPD and FPD groups and direct Sanger sequencing of GBA exons 8–11 and LRRK2 exons 31 and 41 in the LOPD group. In the EOPD and FPD groups, we identified 11 known pathogenic mutations among 15 patients (40.5 %). GBA (E326K, N370S, D409H, L444P) mutations were identified in 7 patients (18.9 %); LRRK2 (p.R1441G and p.G2019S) in 3 patients (8.1 %); biallelic PARK2 mutations (p.N52fs, p.V56E, p.C212Y) in 4 cases (10.8%) and PINK1 homozygous p.G309D in 1 patient (2.7 %). An EOPD patient carried a single PARK2 heterozygous mutation (p.R402C), and another had a novel heterozygous mutation in VPS35 (p.R32S), both of unknown significance. Moreover, pathogenic mutations in GBA (E326K, T369M, N370S, D409H, L444P) and LRRK2 (p.R1441G and p.G2019S) were identified in 13 patients (13.4 %) and 4 patients (4.1 %), respectively, in the LOPD group. A large number of known pathogenic mutations related to PD have been identified. In particular, GBA and LRRK2 mutations appear to be considerably frequent in our population, suggesting a strong Jewish influence. Further research is needed to study the contribution of the novel found mutation p.R32S in VPS35 to the pathogenesis of PD. 2024-04-15T07:06:50Z 2024-04-15T07:06:50Z 2016-01 info:eu-repo/semantics/article Bandrés-Ciga S, Mencacci NE, Durán R, Barrero FJ, Escamilla-Sevilla F, Morgan S, Hehir J, Vives F, Hardy J, Pittman AM. Analysis of the genetic variability in Parkinson's disease from Southern Spain. Neurobiol Aging. 2016 Jan;37:210.e1-210.e5. doi: 10.1016/j.neurobiolaging.2015.09.020. Epub 2015 Oct 8. PMID: 26518746 https://hdl.handle.net/10481/90704 10.1016/j.neurobiolaging.2015.09.020 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional Elservier