title: Analysis of the genetic variability in Parkinson's disease from Southern Spain.
abstract: 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.
authors.affiliation: Department of Physiology, Institute of Neurosciences Federico Olóriz, Centro de Investigacion Biomedica (CIBM), University of Granada, Granada, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Bandrés-Ciga
authors.affiliation: Department of Molecular Neuroscience, Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK.
authors.forename: Niccolò Emmanuele
authors.initials: NE
authors.lastname: Mencacci
authors.affiliation: Department of Physiology, Institute of Neurosciences Federico Olóriz, Centro de Investigacion Biomedica (CIBM), University of Granada, Granada, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Durán
authors.affiliation: Movement Disorders Unit, University Hospital San Cecilio, Granada, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Barrero
authors.affiliation: Movement Disorders Unit, Department of Neurology, Instituto de Investigación Biosanitaria (IBS), University Hospital Virgen de las Nieves, Granada, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Escamilla-Sevilla
authors.affiliation: Department of Molecular Neuroscience, Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Morgan
authors.affiliation: Department of Molecular Neuroscience, Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK.
authors.forename: Jason
authors.initials: J
authors.lastname: Hehir
authors.affiliation: Department of Physiology, Institute of Neurosciences Federico Olóriz, Centro de Investigacion Biomedica (CIBM), University of Granada, Granada, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Vives
authors.affiliation: Department of Molecular Neuroscience, Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.affiliation: Department of Molecular Neuroscience, Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK. Electronic address: a.pittman@ucl.ac.uk.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Pittman
mesh_terms: D000368:Aged; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013030:Spain; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics; D001617:beta-Glucosidase / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; D033921:Vesicular Transport Proteins; D051844:alpha-Synuclein; D001617:beta-Glucosidase; D000099202:PTEN-Induced Putative Kinase; C497604:SNCA protein, human; C419573:VPS35 protein, human; C111567:parkin protein; C495280:LRRK2 protein, human
keywords: Genetics; Mutations; Next-generation sequencing; Parkinson's disease; Southern Spain population