Abstract
Spinocerebellar ataxias (SCAs) represent a diverse group of neurodegenerative disorders characterized by progressive cerebellar ataxia. Diagnostic laboratories in South Korea typically focus on testing for common SCA subtypes, leaving the prevalence of rare SCAs uncertain. This study aimed to explore the prevalence of rare SCA loci, including SCA10, 12, 31, and 36 utilizing molecular techniques including long-read sequencing (LRS). Patients were selected from ataxia cohorts who remained undiagnosed despite testing for common genetic ataxias in Korean (SCA1, 2, 3, 6, 7, 8 17, and dentatorubral-pallidoluysian atrophy), as well as unselected ataxia patients referred for testing common SCAs. Screening for expanded alleles associated with SCA10, 12, 31, and 36 involved techniques such as allele-length PCR, repeat-primed PCR, followed by confirmation through LRS. Among 78 patients from 67 families with undiagnosed cerebellar ataxia despite extensive genetic testing, expanded alleles of SCA36 were identified in 8 families (11.9%) with no detection of SCA10, 12, or 31 alleles. The majority of SCA36 expansions were confirmed by LRS. Furthermore, unselected ataxia patients showed a prevalence of 1.0% for SCA36. Korean SCA36 patients exhibited clinical characteristics similar to global reports, with a higher incidence of hyperreflexia. The study underscores the prevalence of SCA36 in South Korea and emphasizes the potential of LRS as a diagnostic tool for this condition. Integrating LRS into diagnostic protocol could enhance diagnostic efficacy, particularly in populations with a high prevalence of SCA36 like South Korea. Further research is necessary to standardize LRS for routine clinical application.