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

被引:20
作者
Bandres-Ciga, Sara [1 ]
Mencacci, Niccolo Emmanuele [2 ]
Duran, Raquel [1 ]
Javier Barrero, Francisco [3 ]
Escamilla-Sevilla, Francisco [4 ]
Morgan, Sarah [2 ]
Hehir, Jason [2 ]
Vives, Francisco [1 ]
Hardy, John [2 ]
Pittman, Alan M. [2 ]
机构
[1] Univ Granada, Ctr Invest Biomed CIBM, Inst Neurosci Federico Oloriz, Dept Physiol, Granada, Spain
[2] UCL Inst Neurol, Reta Lila Weston Inst Neurol Studies, Dept Mol Neurosci, London WC1N 3BG, England
[3] Univ Hosp San Cecilio, Movement Disorders Unit, Granada, Spain
[4] Univ Hosp Virgen de las Nieves, Inst Invest Biosanitaria IBS, Dept Neurol, Movement Disorders Unit, Granada, Spain
基金
英国医学研究理事会;
关键词
Parkinson's disease; Genetics; Mutations; Southern Spain population; Next-generation sequencing; GLUCOCEREBROSIDASE MUTATIONS; LRRK2; G2019S; ONSET; RISK; PREVALENCE; FEATURES; COMMON;
D O I
10.1016/j.neurobiolaging.2015.09.020
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
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. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码:210.e1 / 210.e5
页数:5
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