Ng, Adeline Su Lyn and Tan, Ai Huey and Tan, Yi Jayne and Lim, Jia Lun and Lian, Michelle Mulan and Dy Closas, Alfand Marl and Ahmad-Annuar, Azlina and Viswanathan, Shanthi and Chia, Yuen Kang and Foo, Jia Nee and Lim, Weng Khong and Tan, Eng-King and Lim, Shen-Yang (2024) Identification of Genetic Variants in Progressive Supranuclear Palsy in Southeast Asia. Movement Disorders, 39 (10). pp. 1829-1842. ISSN 0885-3185, DOI https://doi.org/10.1002/mds.29932.
Full text not available from this repository.Abstract
BackgroundProgressive supranuclear palsy (PSP) is largely a sporadic disease with few reported familial cases. Genome-wide association studies (GWAS) in sporadic PSP in Caucasian populations have identified MAPT as the most commonly associated genetic risk locus with the strongest effect size. At present there are limited data on genetic factors associated with PSP in Asian populations.ObjectivesOur goal was to investigate the genetic factors associated with PSP in Southeast Asian PSP patients.MethodsNext-generation sequencing (whole-exome, whole-genome and targeted sequencing) was performed in two Asian cohorts, comprising 177 PSP patients.ResultsWe identified 17 pathogenic or likely pathogenic variants in 16 PSP patients (9%), eight of which were novel. The most common relevant genetic variants identified were in MAPT, GBA1, OPTN, SYNJ1, and SQSTM1. Other variants detected were in TBK1, PRNP, and ABCA7-genes that have been implicated in other neurodegenerative diseases. Eighteen patients had a positive family history, of whom two carried pathogenic MAPT variants, and one carried a likely pathogenic GBA1 variant. None of the patients had expanded repeats in C9orf72. Furthermore, we found 16 different variants of uncertain significance in 21 PSP patients in PSEN2, ABCA7, SMPD1, MAPT, ATP13A2, OPTN, SQSTM1, CYLD, and BSN.ConclusionsThe genetic findings in our PSP cohorts appear to be somewhat distinct from those in Western populations, and also suggest an overlap of the genetic architecture between PSP and other neurodegenerative diseases. Further functional studies and validation in independent Asian cohorts will be useful for improving our understanding of PSP genetics and guiding genetic screening strategies in these populations. (c) 2024 International Parkinson and Movement Disorder Society. In a study of 182 progressive supranuclear palsy (PSP) patients from Asian cohorts, 17 pathogenic/likely pathogenic variants were identified in 16 PSP patients (9%), 8 of which were novel. The genetic findings in the Asian PSP cohorts differ from those in Western populations, and suggest an overlap in genetic architecture between PSP and other neurodegenerative diseases.image
| Item Type: | Article |
|---|---|
| Funders: | Ministry of Higher Education Malaysia Fundamental Research Grant Scheme (FRGS/1/2020/SKK0/UM/01/2), University of Malaya Parkinson's Disease and Movement Disorders Research Program (PV035-2017), Singapore Ministry of Health's National Medical Research Council Open Fund Individual Research Grant (MOH-000559), Ministry of Education, Singapore (MOE-T2EP30220-0005) ; (MOE-MOET32020-0004), Open Fund Large Collaborative Grant (MOH-OFLCG18May-0002), Singapore Translational Research (STaR) Investigator Award (NMRC/STaR/0030/2018), Clinician-Scientist Award (MOH-CSAINV21-0005) ; (MOH-TA18may-0003), Precision Medicine Research, Singapore (MOH-000588) |
| Subjects: | R Medicine > R Medicine (General) |
| Divisions: | Faculty of Medicine > Biomedical Science Department Faculty of Medicine > Medicine Department |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 07 Feb 2025 07:00 |
| Last Modified: | 07 Feb 2025 07:00 |
| URI: | http://eprints.um.edu.my/id/eprint/47524 |
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