ClinVar

Moseley et al. (2006) identified IC2-immunoreactive intranuclear inclusions, detecting polyglutamine expansions, in brain tissue from patients with spinocerebellar ataxia-8 (SCA8; 608768), but not in normal controls. The polyglutamine protein was determined to be ATXN8 resulting from an expanded CAG repeat. A complementary expanded CTG repeat in the opposite strand, encoded by the ATXN8OS gene (603680.0001), was identified in patients with SCA8 and shown to result in transcription of a toxic mRNA with an expanded CUG repeat (Koob et al., 1999). Thus, the findings of Moseley et al. (2006) indicated that bidirectional transcription at the SCA8 locus results in expression of both a polyglutamine protein and a CUG expansion transcript, which may represent a toxic gain of function at both the protein and RNA levels.