| CAG repeat expansion | The pathogenic mutation is an expanded CAG trinucleotide repeat in the ATXN1 gene on chromosome 6p22-23 |
| Normal alleles | 6-35 CAG repeats |
| Intermediate alleles (premutation) | 36-38 repeats (may expand in meiosis) |
| Full mutation alleles | 39-83+ repeats (disease-causing) |
| Anticipation | Larger repeats correlate with earlier onset and more severe disease |
| Normal function | Ataxin-1 is a transcriptional regulator involved in RNA splicing and neuronal gene expression |
| Pathogenic mechanism | The expanded polyglutamine tract causes toxic gain-of-function, leading to protein misfolding, aggregation, and cellular dysfunction |
| Selective vulnerability | Purkinje cells in the cerebellum and neurons in the inferior olive are particularly susceptible to ataxin-1 toxicity |
| Cerebellar atrophy | Severe loss of Purkinje cells and granular layer neurons |
| Inferior olivary nucleus degeneration | Neuronal loss in the inferior olive |
| Brainstem involvement | Degeneration of cranial nerve nuclei |
| Spinal cord pathology | Loss of neurons in the posterior columns and anterior horns |
| Databases | OMIMOrphanetClinicalTrialsPubMed |