Staff View: Clinical phenotype of LRRK2R1441C in 2 Chinese sisters

Clinical phenotype of LRRK2R1441C in 2 Chinese sisters

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, No...

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Main Authors:	Lim, Shen-Yang, Lim, Jia Lun, Ahmad-Annuar, Azlina, Lohmann, Katja, Tan, Ai Huey, Lim, Kai Bin, Tay, Yi Wen, Shing, Yee Lee, Muthusamy, Kalai Arasu, Bauer, Peter, Rolfs, Arndt, Klein, Christine
Format:	Article
Published:	Karger 2020
Subjects:	RC Internal medicine RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Online Access:	http://eprints.um.edu.my/31664/
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spelling	my.um.eprints.316642022-10-20T07:30:17Z http://eprints.um.edu.my/31664/ Clinical phenotype of LRRK2R1441C in 2 Chinese sisters Lim, Shen-Yang Lim, Jia Lun Ahmad-Annuar, Azlina Lohmann, Katja Tan, Ai Huey Lim, Kai Bin Tay, Yi Wen Shing, Yee Lee Muthusamy, Kalai Arasu Bauer, Peter Rolfs, Arndt Klein, Christine RC Internal medicine RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry 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. Karger 2020-10 Article PeerReviewed 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 of LRRK2R1441C in 2 Chinese sisters. Neurodegenerative Diseases, 20 (1). pp. 39-45. ISSN 1660-2854, DOI https://doi.org/10.1159/000508131 <https://doi.org/10.1159/000508131>. 10.1159/000508131
institution	Universiti Malaya
building	UM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Malaya
content_source	UM Research Repository
url_provider	http://eprints.um.edu.my/
topic	RC Internal medicine RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
spellingShingle	RC Internal medicine RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry Lim, Shen-Yang Lim, Jia Lun Ahmad-Annuar, Azlina Lohmann, Katja Tan, Ai Huey Lim, Kai Bin Tay, Yi Wen Shing, Yee Lee Muthusamy, Kalai Arasu Bauer, Peter Rolfs, Arndt Klein, Christine Clinical phenotype of LRRK2R1441C in 2 Chinese sisters
description	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.
format	Article
author	Lim, Shen-Yang Lim, Jia Lun Ahmad-Annuar, Azlina Lohmann, Katja Tan, Ai Huey Lim, Kai Bin Tay, Yi Wen Shing, Yee Lee Muthusamy, Kalai Arasu Bauer, Peter Rolfs, Arndt Klein, Christine
author_facet	Lim, Shen-Yang Lim, Jia Lun Ahmad-Annuar, Azlina Lohmann, Katja Tan, Ai Huey Lim, Kai Bin Tay, Yi Wen Shing, Yee Lee Muthusamy, Kalai Arasu Bauer, Peter Rolfs, Arndt Klein, Christine
author_sort	Lim, Shen-Yang
title	Clinical phenotype of LRRK2R1441C in 2 Chinese sisters
title_short	Clinical phenotype of LRRK2R1441C in 2 Chinese sisters
title_full	Clinical phenotype of LRRK2R1441C in 2 Chinese sisters
title_fullStr	Clinical phenotype of LRRK2R1441C in 2 Chinese sisters
title_full_unstemmed	Clinical phenotype of LRRK2R1441C in 2 Chinese sisters
title_sort	clinical phenotype of lrrk2r1441c in 2 chinese sisters
publisher	Karger
publishDate	2020
url	http://eprints.um.edu.my/31664/
_version_	1748181063663878144
score	13.211869

Clinical phenotype of LRRK2R1441C in 2 Chinese sisters

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