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Analysis of the genetic variability in Parkinson's disease from Southern Spain.
Neurobiol Aging 2016; 37:210.e1-210.e5NA

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+Show Affiliations

Department of Physiology, Institute of Neurosciences Federico Olóriz, Centro de Investigacion Biomedica (CIBM), University of Granada, Granada, Spain.Department of Molecular Neuroscience, Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK.Department of Physiology, Institute of Neurosciences Federico Olóriz, Centro de Investigacion Biomedica (CIBM), University of Granada, Granada, Spain.Movement Disorders Unit, University Hospital San Cecilio, Granada, Spain.Movement Disorders Unit, Department of Neurology, Instituto de Investigación Biosanitaria (IBS), University Hospital Virgen de las Nieves, Granada, Spain.Department of Molecular Neuroscience, Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK.Department of Molecular Neuroscience, Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK.Department of Physiology, Institute of Neurosciences Federico Olóriz, Centro de Investigacion Biomedica (CIBM), University of Granada, Granada, Spain.Department of Molecular Neuroscience, Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK.Department of Molecular Neuroscience, Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK. Electronic address: a.pittman@ucl.ac.uk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26518746

Citation

Bandrés-Ciga, Sara, et al. "Analysis of the Genetic Variability in Parkinson's Disease From Southern Spain." Neurobiology of Aging, vol. 37, 2016, pp. 210.e1-210.e5.
Bandrés-Ciga S, Mencacci NE, Durán R, et al. Analysis of the genetic variability in Parkinson's disease from Southern Spain. Neurobiol Aging. 2016;37:210.e1-210.e5.
Bandrés-Ciga, S., Mencacci, N. E., Durán, R., Barrero, F. J., Escamilla-Sevilla, F., Morgan, S., ... Pittman, A. M. (2016). Analysis of the genetic variability in Parkinson's disease from Southern Spain. Neurobiology of Aging, 37, pp. 210.e1-210.e5. doi:10.1016/j.neurobiolaging.2015.09.020.
Bandrés-Ciga S, et al. Analysis of the Genetic Variability in Parkinson's Disease From Southern Spain. Neurobiol Aging. 2016;37:210.e1-210.e5. PubMed PMID: 26518746.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of the genetic variability in Parkinson's disease from Southern Spain. AU - Bandrés-Ciga,Sara, AU - Mencacci,Niccolò Emmanuele, AU - Durán,Raquel, AU - Barrero,Francisco Javier, AU - Escamilla-Sevilla,Francisco, AU - Morgan,Sarah, AU - Hehir,Jason, AU - Vives,Francisco, AU - Hardy,John, AU - Pittman,Alan M, Y1 - 2015/10/08/ PY - 2015/07/23/received PY - 2015/09/08/revised PY - 2015/09/26/accepted PY - 2015/11/1/entrez PY - 2015/11/1/pubmed PY - 2016/9/27/medline KW - Genetics KW - Mutations KW - Next-generation sequencing KW - Parkinson's disease KW - Southern Spain population SP - 210.e1 EP - 210.e5 JF - Neurobiology of aging JO - Neurobiol. Aging VL - 37 N2 - 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. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/26518746/Analysis_of_the_genetic_variability_in_Parkinson's_disease_from_Southern_Spain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(15)00477-7 DB - PRIME DP - Unbound Medicine ER -