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

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.