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

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Abstract
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.

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