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Fulltext New insights from a Malaysian real-world deep brain stimulation cohort

Dy Closas AMF, Tan AH, Tay YW, Hor JW, Toh TS, Lim JL, et al.

J Parkinsons Dis, 2025 Feb;15(1):189-201.
PMID: 39973484 DOI: 10.1177/1877718X241297715

BackgroundThe availability of deep brain stimulation (DBS), a highly efficacious treatment for several movement disorders, remains low in developing countries, with scarce data available on utilization and outcomes.ObjectiveWe characterized the DBS cohort and outcomes at a Malaysian quaternary medical center.MethodsA retrospective chart review was done on DBS-related surgery at the University of Malaya, including clinico-demographic, genetics, and outcomes data focusing on post-operative medication reduction and complications.Results149 Parkinson's disease (PD) patients underwent DBS targeting the subthalamic nucleus. Six had globus pallidus internus DBS (primarily for dystonia). Only 16.1% of patients were government-funded. Of the 133 PD patients operated in the past decade (2013-2022), 25 (18.8%) had disease duration <5 years. At 6-12 months post-DBS, median levodopa-equivalent daily dose (LEDD) reduction was 440.5 [418.9] mg/day, corresponding to a reduction of ≥50% and ≥30% in 42.2% and 69.8% of patients, respectively. LEDD reductions were larger in the early-onset and short-duration subgroups. Three patients (1.9% of 155) had symptomatic intracranial hemorrhage, resulting in stroke in two. Pathogenic monogenic or GBA1 variants were detected in 12/76 (16%) of patients tested, mostly comprising the "severe" GBA1 variant p.L483P (12%).ConclusionsThis is the largest report on DBS from Southeast Asia. The procedures were effective, and complication rates on par with international norms. Our study found a high frequency of GBA1-PD; and included a substantial number of patients with short-duration PD, who had good outcomes. It also highlights regional inequities in access to device-aided therapy.
GCH1 p.Ser80Asn Confers Risk for Parkinson's Disease in East Asian Populations

Tay YW, Lee AL, Schee JP, Lin CH, Tan EK, Shin JH, et al.

Mov Disord, 2026 Oct 14.
PMID: 42876073 DOI: 10.1002/mds.70530

INTRODUCTION: GCH1 has been implicated in Parkinson's disease (PD), but its risks variants and associations are not well defined.
OBJECTIVES: Our goal was to investigate the clinical relevance and PD risk associated with the GCH1 p.Ser80Asn variant.
METHODS: We first identified a segregating GCH1 p.Ser80Asn variant in a Malaysian Chinese PD family via whole genome sequencing (WGS). We assessed its risk association using multi-ancestry WGS data from the Global Parkinson's Genetics Program (GP2) (n = 22,372PD vs. n = 8,826Controls) and meta-analysis of East Asian (EAS) cohorts (n = 4,712PD vs. 38,733Controls). Haplotype analyses were performed and clinico-demographic details of affected variant carriers were collated.
RESULTS: The GCH1 p.Ser80Asn variant was enriched in GP2 EAS PD populations (n = 9/2,757; 0.33%), but not detected in other ancestries. Meta-analysis revealed increased PD risk in EAS populations (odds ratio = 5.1; 95% confidence intervals [CI] = 2.3-10.7; P = 2.89 × 10-5). A shared haplotype (~330 kbp) was identified among variant carriers. Affected carriers (mean age at onset: 56.3 ± 12.5 years) had additional occurrence of dystonia, whereas dementia was rare.
CONCLUSIONS: The GCH1 p.Ser80Asn variant is a rare, EAS-enriched risk variant for PD. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Fulltext GCH1 p.Ser80Asn Confers Risk for Parkinson's Disease in East Asian Populations

Tay YW, Lee AL, Schee JP, Lin CH, Tan EK, Shin JH, et al.

medRxiv, 2026 Jun 22.
PMID: 42396327 DOI: 10.64898/2026.06.11.26354827

INTRODUCTION: GCH1 has been implicated in Parkinson's disease (PD), but its risks variants and associations are not well defined.
OBJECTIVES: To investigate the clinical relevance and PD risk associated with the GCH1 p.Ser80Asn variant.
METHODS: We first identified a segregating GCH1 p.Ser80Asn variant in a Malaysian Chinese PD family via whole genome sequencing (WGS). We assessed its risk association using multi-ancestry WGS data from the Global Parkinson's Genetics Program (GP2) (n=22,372PD vs n=8,826Controls) and meta-analysis of East Asian (EAS) cohorts (n=4,712PD vs 38,733Controls). Clinico-demographic details of affected variant carriers were collated.
RESULTS: The GCH1 p.Ser80Asn variant was enriched in GP2 EAS PD populations (n=9/2,757; 0.33%) but not detected in other ancestries. Meta-analysis revealed increased PD risk in EAS populations (odds ratio:5.1; 95%CI:2.3-10.7; p=2.89×10-5). Affected carriers (mean age at onset:56.3±12.5 years) had additional occurrence of dystonia, while dementia was rare.
CONCLUSIONS: The GCH1 p.Ser80Asn variant is a rare, EAS-enriched risk variant for PD.
Exome Sequencing Identifies Population-Specific Genetic Risk Factors for Progressive Supranuclear Palsy in Asia

Chen PS, Lin RJ, Chen HY, Cheng L, Hung MZ, Lee NC, et al.

Mov Disord, 2026 Nov 01.
PMID: 42967813 DOI: 10.1002/mds.70595

BACKGROUND: Progressive supranuclear palsy (PSP) is a debilitating primary tauopathy. Although genome-wide association studies have identified risk loci in European populations, the genetic architecture of PSP in Asia remains largely undefined.
OBJECTIVES: We aimed to identify population-specific genetic risk factors in Asian patients with PSP.
METHODS: We performed whole-exome sequencing in 549 patients with PSP recruited across East and Southeast Asia. Variant frequencies were compared with 1492 whole-genome-sequenced controls from the Taiwan Biobank. Novel variants were functionally evaluated using cellular and Drosophila models.
RESULTS: Among 549 patients (mean age at onset 65.1 ± 7.4 years; 60.47% male), 29 (5.28%) carried heterozygous pathogenic or likely pathogenic variants, including 12 novel variants. Additionally, 127 patients (23.13%) harbored 144 rare variants of uncertain significance with minor allele frequency