Lim, Shen-Yang and Lim, Jia Lun and Ahmad-Annuar, Azlina and Lohmann, Katja and Tan, Ai Huey and Lim, Kai Bin and Tay, Yi Wen and Shing, Yee Lee and Muthusamy, Kalai Arasu and Bauer, Peter and Rolfs, Arndt and Klein, Christine (2020) Clinical phenotype ofLRRK2R1441C in 2 Chinese sisters. Neurodegenerative Diseases, 20 (1). pp. 39-45. ISSN 1660-2854, DOI https://doi.org/10.1159/000508131.
Full text not available from this repository.Abstract
Pathogenic and risk variants in theLRRK2gene are among the main genetic contributors to Parkinson's disease (PD) worldwide, and LRRK2-targeted therapies for patients with PARK-LRRK2are now entering clinical trials. However, in contrast to theLRRK2G2019S mutation commonly found in Caucasians, North-African Arabs, and Ashkenazi Jews, relatively little is known about other causativeLRRK2mutations, and data on genotype-phenotype correlations are largely lacking. This report is from an ongoing multicentre study in which next-generation sequencing-based PD gene panel testing has so far been conducted on 499 PD patients of various ethnicities from Malaysia. We describe 2 sisters of Chinese ancestry with PD who carry the R1441C mutation inLRRK2(which in Asians has been reported in only 2 Chinese patients previously), and highlight interesting clinical observations made over a decade of close follow-up. We further explored the feasibility of using a brief, expert-administered rating scale (the Clinical Impression of Severity Index; CISI-PD) to capture data on global disease severity in a large (n= 820) unselected cohort of PD patients, including severely disabled individuals typically excluded from research studies. All patients in this study were managed and evaluated by the same PD neurologist, and these data were used to make broad comparisons between the monogenic PD cases versus the overall ``real world'' PD cohort. This report contributes to the scarce literature on R1441C PARK-LRRK2, offering insights into natural history and epidemiological aspects, and provides support for the application of a simple and reliable clinical tool that can improve the inclusion of under-represented patient groups in PD research.
| Item Type: | Article |
|---|---|
| Funders: | University of Malaya Parkinson's Disease and Movement Disorder Research Program [Grant No: PV035-2017], Ministry of Education, Malaysia [Grant No: FRGS/1/2018/SKK08/UM/02/3], German Research Foundation [Grant No: (DFG) FOR2488] |
| Uncontrolled Keywords: | Parkinson's disease; LRRK2; R1441C; Asian subjects; Genetics; CISI-PD; Rating scales; Deep brain stimulation |
| Subjects: | R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry |
| Divisions: | Faculty of Medicine |
| Depositing User: | Ms Zaharah Ramly |
| Date Deposited: | 26 Nov 2024 08:20 |
| Last Modified: | 26 Nov 2024 08:20 |
| URI: | http://eprints.um.edu.my/id/eprint/36371 |
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