Clinical, neuropathological, and molecular study in two families with spinocerebellar ataxia type 6 (SCA6)

To clarify the clinical, neuropathological, and molecular characteristics o f spinocerebellar ataxia type 6 (SCA6), two unrelated Japanese families wit h SCA6 were studied. A clinical feature of the two families was late onset "pure" cerebellar ataxia. Pathologically, three SCA6 brains consistently sh owed Purkinje cell dominant cortical cerebellar degeneration. Morphometric analysis showed that loss of the cerebellar granule cells and inferior oliv ary neurons were very mild compared with the severity of Purkinje cell loss . There was no obvious ubiquitin immunoreactive nuclear inclusions. All aff ected patients had identical expanded alleles, and the expansion was also h omogeneously distributed throughout the brain without mosaicism. The presen t study showed that SCA6 is characterised by Purkinje cell dominant cortica l cerebellar degeneration, highly stable transmission of the CAG repeat exp ansion, and lack of ubiquitin immunoreactive nuclear inclusions.