Expanded ATXN10 Alleles in Neurodegenerative Disorders: A Case Series and Review of the Literature

Cornejo-Olivas M.; Raney A.; Abad A.; Sedov K.; Sarapura-Castro E.; Sosa H.M.; Manrique-Enciso C.; Torres C.A.M.; Illanes-Manrique M.; Dolzhenko E.; Rivera-Valdivia A.; Qiao W.; Schüle B. · Movement Disorders Clinical Practice (2026) · DOI: 10.1002/mdc3.70765

Resumen

Background: Spinocerebellar ataxia type 10 (SCA10 or ATX-ATXN10) is typically attributed to large intronic ATTCT repeat expansions in ATXN10, yet interpretation is complicated by repeat interruptions, reduced penetrance, and assay limitations. Cases: We describe three patients referred for SCA10 evaluation in whom ATXN10 repeat-primed PCR (RP-PCR) reported “>32 repeats, probable pathogenic.” Targeted long-read sequencing (LRS) identified two individuals with intermediate, mixed repeat tracts (~100–150 repeats) and one individual with a very large, highly pure ATTCT expansion (~1127 repeats). Each phenotype was explained by an alternative disorder: spastic ataxia syndrome caused by biallelic pathogenic FA2H variants (HSP/ATX-FA2H), full-penetrance ATXN3 CAG expansion consistent with SCA3/ATX-ATXN3, and clinically established MSA-C. Literature Review: We identified three studies reporting four ATX-ATXN10 cases coexisting with Huntington's disease (one case) and SCA2/ATX-ATXN2 (three cases). Conclusion: Our three cases suggest that intermediate ATXN10 alleles in the 100–150 range may not be pathogenic and large ATXN10 expansions remain probably pathogenic in most patients with a compatible autosomal-dominant ataxia phenotype. Comprehensive genetic testing beyond RP-PCR is necessary for accurate diagnosis.

Instituciones: Universidad Científica del Sur