ATXN2 polyglutamine intermediate repeats length expansions in Malaysian patients with amyotrophic lateral sclerosis (ALS)

Document Type

Article

Publication Date

1-1-2025

Abstract

Intermediate CAG repeats from 29 to 33 in the ATXN2 gene contributes to the risk of amyotrophic lateral sclerosis (ALS) in European and Asian populations. In this study, 148 ALS patients of multiethnic descent: Chinese (56.1%), Malay (24.3%), Indian (12.8%), others (6.8%) and 100 neurologically normal controls were screened for the ATXN2 CAG repeat expansion. The most common repeat length in both the controls and patients was 22. No familial ALS patients were positive for the intermediate repeat sizes (29-33), while four sporadic patients (2.8%) were positive, with one harbouring a rare ATXN2 homozygous 32 repeat expansion, and a likely pathogenic variant in SPAST. All four patients had limb-onset ALS. Despite representing the smallest ethnic group in our patient cohort, three of the four patients with intermediate repeat sizes were of Indian ancestry. This study, which is the first in Malaysia and Southeast Asia, shows that ATXN2 intermediate risk expansions are relevant to ALS in these populations and will help to inform future genetic testing strategies in the clinic.

Keywords

Amyotrophic lateral sclerosis, ATXN2, Intermediate repeat length, Homozygous repeat expansion, Malaysia

Divisions

biomedsc,medicinedept

Funders

Malaysian Ministry of Education Fundamental Research Grant Scheme

Publication Title

Neurogenetics

Volume

26

Issue

1

Publisher

Springer

Publisher Location

ONE NEW YORK PLAZA, SUITE 4600, NEW YORK, NY, UNITED STATES

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