Characteristic <scp>RNA</scp> foci of the abnormal hexanucleotide <scp>GGCCUG</scp> repeat expansion in spinocerebellar ataxia type 36 (<scp>A</scp>sidan)

<jats:sec><jats:title>Background and purpose</jats:title><jats:p>Spinocerebellar ataxia type 36 (<jats:styled-content style="fixed-case">SCA</jats:styled-content>36), also called Asidan, is an autosomal‐dominant neurodegenerative disorder identified as a hexanucleotide <jats:styled-content style="fixed-case">GGCCTG</jats:styled-content> repeat expansion in the first intron 1 of the <jats:italic><jats:styled-content style="fixed-case">NOP</jats:styled-content>56</jats:italic> gene. In the present study, for the first time an autopsy sample from an <jats:styled-content style="fixed-case">A</jats:styled-content>sidan patient was examined and cytoplasmic inclusions and (<jats:styled-content style="fixed-case">GGCCUG</jats:styled-content>)<jats:sub><jats:italic>n</jats:italic></jats:sub> repeat <jats:styled-content style="fixed-case">RNA</jats:styled-content> foci were detected.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Hematoxylin and eosin staining, immunohistochemical staining, as well as fluorescence <jats:italic>in situ</jats:italic> hybridization were used to investigate the cytoplasmic inclusions of ubiquitin and p62 and the (<jats:styled-content style="fixed-case">GGCCUG</jats:styled-content>)<jats:sub><jats:italic>n</jats:italic></jats:sub> repeat <jats:styled-content style="fixed-case">RNA</jats:styled-content> foci.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The present study showed both ubiquitin‐ and p62‐positive inclusions in the cytoplasm of the inferior olivary nucleus of the <jats:styled-content style="fixed-case">A</jats:styled-content>sidan patient, (<jats:styled-content style="fixed-case">GGCCUG</jats:styled-content>)<jats:sub><jats:italic>n</jats:italic></jats:sub> <jats:styled-content style="fixed-case">RNA</jats:styled-content> foci in neuronal nuclei of the cerebrum, cerebellum, inferior olive, spinal cord and temporal muscle, and three types of <jats:styled-content style="fixed-case">RNA</jats:styled-content> foci, i.e. single small, multiple small and giant. Of interest is that the giant <jats:styled-content style="fixed-case">RNA</jats:styled-content> foci, nearly 10 μm in diameter, that were detected in <jats:styled-content style="fixed-case">P</jats:styled-content>urkinje cells, spinal motor neurons and most frequently in the inferior olivary nucleus, may be responsible for pivotal clinical symptoms of <jats:styled-content style="fixed-case">A</jats:styled-content>sidan.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The present study is the first report to show neuronal cytoplasmic inclusion bodies and giant <jats:styled-content style="fixed-case">RNA</jats:styled-content> foci in an <jats:styled-content style="fixed-case">A</jats:styled-content>sidan patient. The relationships between the giant <jats:styled-content style="fixed-case">RNA</jats:styled-content> foci and neurodegeneration have yet to be studied.</jats:p></jats:sec>