Analysis of the genetic variability in Parkinson's disease from Southern Spain

Sara Bandrés-Ciga, Niccolò Emmanuele Mencacci, Raquel Durán, Francisco J avier Barrero, Francisco Escamilla-Sevilla, Sarah Morgan, Jason Hehir, Francisco Vives, John Hardy, Alan M. Pittman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)210.e1-210.e5
JournalNeurobiology of Aging
Volume37
DOIs
StatePublished - Jan 1 2016

Keywords

  • Genetics
  • Mutations
  • Next-generation sequencing
  • Parkinson's disease
  • Southern Spain population

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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