Long-read sequencing identifies ATXN3 repeat expansions, and transcriptomics reveals disease progression biomarkers and druggable targets for spinocerebellar ataxia type 3.

ABSTRACT:

Background

Hereditary ataxias (HAs) are neurodegenerative disorders characterized by progressive cerebellar degeneration, with autosomal dominant spinocerebellar ataxias (SCAs) representing the most prevalent subtype. SCA3, the most common form worldwide, is caused by CAG repeat expansions in ATXN3, resulting in pathogenic ataxin-3 aggregation. However, the underlying molecular mechanisms driving disease progression remain incompletely understood.

Methods

We utilized an integrated multi-omics strategy to investigate a five-generation Chinese HA pedigree. Genetic analyses included targeted ataxia panel sequencing (TS), whole-exome sequencing (WES), and long-read whole-genome sequencing (LR-WGS) of blood-derived DNA to identify causal variants and confirm diagnosis. Transcript

SUBMITTER: Liu C 

PROVIDER: S-EPMC12403609 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature