The human genome contains two<unk> n genes; DRPLA has been correlated to the expansion of the polyglutamine region of the<unk> n-1 gene on chromosome 12p13.3. A normal number of CAG repeats in the<unk> n-1 gene is 7–34, affected individuals display 49–93 repeats. DRPLA displays anticipation (earlier age of onset for subsequent generations) and an inverse correlation between the size of the expanded CAG repeat and the age of symptom onset. Paternal transmission results in more prominent anticipation (26–29 years) than maternal transmission (14–15 years).<unk> n-1<unk> n-1 (ATN1) encodes a hydrophilic 1184 amino acid protein with several repetitive motifs including a serine-rich region, a variable length polyglutamine tract, a polyproline tract, and a region of alternating acidic and basic residues. It contains a putative nuclear localization signal in the N-terminus of the protein and a putative nuclear export signal in the C-terminus. ATN1 is ubiquitously expressed in all tissues, but proteolytically cleaved in neuronal cells. The function of ATN1 is not clear, however it is believed to be a transcriptional co-repressor. ATN1 and<unk> n-2 can be co-immunoprecipitated, indicating that they may carry out some functions together in a molecular complex.<unk> n-1 may be a dispensable or redundant protein as mice bred with a null allele for<unk> n-1 produce viable and fertile offspring and show no compensatory upregulation of<unk> n-2. Transgenic mouse models Mouse models of DRPLA have been successfully generated, which demonstrate the same intergenerational instability and severe phenotype as human DRPLA. The Schilling mice express full-length human<unk> n-1 with 65 CAG repeats under transcriptional control of the mouse prion protein promoter. The mice demonstrated progressive ataxia, tremors, abnormal movements, seizures and premature death. Like in human brains, nuclear accumulation was demonstrated and occasional NIIs were visualised, but the NIIs did not stain for ubiquitin and no neuronal loss was seen. The Sato mice harbored a single copy of full-length human<unk> n-1 with 76 or 129 CAG repeats. The hemizygous transgenic offspring of the Q129 mice exhibited symptoms similar to juvenile-type DRPLA, such as myoclonus and seizures. Again, neuronal<unk>  was noted, but no neuronal loss (until death). Diffuse accumulation in the nuclei began on post-natal day 4 and ubiquitinated NII formation was detectable at 9 weeks of age. No PML bodies were found to be associated with the NIIs, which were morphologically mildly altered from those seen in human neural cells.
Dentatorubral–pallidoluysian atrophy
Cerebellar abiotrophy
Central chromatolysis
Corticobasal degeneration
Olivopontocerebellar atrophy
Spinal muscular atrophy with lower extremity predominance 1
Cerebellar degeneration
Multi/minicore myopathy