Another common genetic ataxia in South Korea: Spinocerebellar ataxia 36

Spinocerebellar ataxias (SCAs) represent a diverse group of neurodegenerative disorders characterized by progressive cerebellar ataxia. In South Korea, diagnostic laboratories typically focus on common SCA subtypes, leaving the prevalence of rare SCAs uncertain. This study aimed to explore the frequency of rarer forms of SCA, including SCA10, 12, 31, and 36 utilizing molecular techniques including long-read sequencing (LRS). Patients from ataxia cohorts who remained undiagnosed after testing for common genetic ataxias (SCA1, 2, 3, 6, 7, 8 17, and dentatorubral-pallidoluysian atrophy) were analyzed, along with unselected ataxia patients referred for screening of common SCAs. Expanded alleles for SCA10, 12, 31, and 36 were investigated through allele-length PCR, repeat-primed PCR, and LRS. Among 78 patients from 67 families with undiagnosed cerebellar ataxia, SCA36 was identified in 8 families (11.9%), while SCA10, 12, or 31 were not found. In unselected ataxia, SCA36 was present in 1.0% (1/99). Korean SCA36 patients exhibited clinical characteristics similar to global reports, with a higher incidence of hyperreflexia. The haplotype of expanded alleles identified in LRS was consistent among SCA36 patients. The findings indicate that SCA36 accounts for 11.9% of diagnoses after excluding common SCAs and 1.0% in unselected ataxia patients. 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.