UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

LRRK2 Mutations and Asian Disease-Associated Variants in the First Parkinson's Disease Cohort from Kazakhstan

Kaiyrzhanov, R; Aitkulova, A; Shashkin, C; Zharkinbekova, N; Rizig, M; Zholdybayeva, E; Jarmukhanov, Z; ... Houlden, H; + view all (2020) LRRK2 Mutations and Asian Disease-Associated Variants in the First Parkinson's Disease Cohort from Kazakhstan. Parkinson's Disease , Article 2763838. 10.1155/2020/2763838. Green open access

[thumbnail of 2763838.pdf] Text
2763838.pdf - Published version

Download (1MB)

Abstract

BACKGROUND: LRRK2 mutations have emerged as the most prevalent and potentially treatable determinants of Parkinson’s disease (PD). Peculiar geographic distribution of these mutations has triggered an interest in genotyping PD cohorts of different ethnic backgrounds for LRRK. OBJECTIVE: Here, we report on the results of LRRK2 screening in the first Central Asian PD cohort. METHODS: 246 PD patients were consecutively recruited by movement disorder specialists from four medical centers in Kazakhstan, and clinicodemographic data and genomic DNA from blood were systematically obtained and shipped to the Institute of Neurology University College London together with DNAs from 200 healthy controls. The cohort was genotyped for five LRRK2 mutations (p.Gly2019Ser, p.Arg1441His, p.Tyr1699Cys, p.Ile2020Thr, and p.Asn1437His) and three East Asian disease-associated variants (p.Gly2385Arg, p.Ala419Val, and p.Arg1628Pro) via Kompetitive allele-specific polymerase chain reaction assay analysis. RESULTS: None of the study subjects carried LRRK2 mutations, whereas the following Asian variants were found with insignificant odds ratios (OR): p.Gly2385Arg (1.2%, minor allele frequency (MAF) 0.007, OR 1.25, ), p.Ala419Val (3.7%, MAF 0.02, OR 1.5, ), and p.Arg1628Pro was found only in 1% of controls. p.Gly2385Arg was positive in a big family with PD and tremor, although with incomplete segregation. One early-onset PD subject was homozygous for p.Ala419Val who developed fast progression and severe dyskinesias. p.Ala419Val was associated with early-onset PD. CONCLUSIONS: We showed that East Asian LRRK variants could be found in Central Asian populations but their pathogenicity remains to be elucidated in larger PD cohorts.

Type: Article
Title: LRRK2 Mutations and Asian Disease-Associated Variants in the First Parkinson's Disease Cohort from Kazakhstan
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1155/2020/2763838
Publisher version: https://doi.org/10.1155/2020/2763838
Language: English
Additional information: © 2020 Rauan Kaiyrzhanov et al. This is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10093470
Downloads since deposit
20Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item