In:
Neurodegenerative Diseases, S. Karger AG, Vol. 20, No. 1 ( 2020), p. 39-45
Kurzfassung:
Pathogenic and risk variants in the 〈 i 〉 LRRK2 〈 /i 〉 gene are among the main genetic contributors to Parkinson’s disease (PD) worldwide, and LRRK2-targeted therapies for patients with PARK- 〈 i 〉 LRRK2 〈 /i 〉 are now entering clinical trials. However, in contrast to the 〈 i 〉 LRRK2 〈 /i 〉 G2019S mutation commonly found in Caucasians, North-African Arabs, and Ashkenazi Jews, relatively little is known about other causative 〈 i 〉 LRRK2 〈 /i 〉 mutations, 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 in 〈 i 〉 LRRK2 〈 /i 〉 (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 ( 〈 i 〉 n 〈 /i 〉 = 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- 〈 i 〉 LRRK2 〈 /i 〉 , 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.
Materialart:
Online-Ressource
ISSN:
1660-2854
,
1660-2862
Sprache:
Englisch
Verlag:
S. Karger AG
Publikationsdatum:
2020
ZDB Id:
2126858-7
