The genetic landscape of spinocerebellar ataxias in Taiwan: Insights from 876 genetically confirmed cases.

BACKGROUND

Spinocerebellar ataxias (SCAs) are a group of inherited neurodegenerative disorders characterized by progressive cerebellar dysfunction and variable neurological features. Although the distribution and genetic characteristics of SCA subtypes differ across populations, comprehensive data from Taiwan have been limited. This study aimed to update the genetic landscape of SCAs in Taiwan by investigating subtype frequencies, repeat expansion patterns, and genotype-phenotype correlations in a large single-center cohort.

METHODS

We retrospectively analyzed clinical and genetic data from 876 patients with genetically confirmed SCA1, SCA2, SCA3, SCA6, SCA8, or dentatorubral-pallidoluysian atrophy (DRPLA), evaluated at a national referral center over a 25-year period.

RESULTS

SCA3 was the most prevalent subtype (56.6 %), followed by SCA2 (20.0 %) and SCA6 (10.3 %). Among all subtypes, a significant inverse correlation between repeat expansion size and age at onset was observed, with the strongest association in DRPLA (R2 = 0.73, p = 5.1 × 10-5) and weakest in SCA8 (R2 = 0.32, p = 8.3 × 10-4). SCA6 showed a narrow repeat size range (21-29 repeats), while SCA8 displayed the widest range (64-189 repeats) with some alleles exceeding PCR detection limits. Family clustering patterns varied, with SCA8 having the highest proportion of sporadic cases (70.2 %), likely reflecting reduced penetrance and genetic complexity.

CONCLUSION

This study provides an updated genetic landscape of SCAs in Taiwan. Subtype-specific differences in repeat size, onset age, and inheritance patterns offer clinically valuable insights for diagnosis, genetic counseling, and future studies targeting disease-modifying factors in repeat expansion SCAs.