Characteristic RNA foci of the abnormal hexanucleotide GGCCUG repeat expansion in spinocerebellar ataxia type 36 (Asidan)

W. Liu, Y. Ikeda, Nozomi Hishikawa, Toru Yamashita, K. Deguchi, Koji Abe

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background and purpose: Spinocerebellar ataxia type 36 (SCA36), also called Asidan, is an autosomal-dominant neurodegenerative disorder identified as a hexanucleotide GGCCTG repeat expansion in the first intron 1 of the NOP56 gene. In the present study, for the first time an autopsy sample from an Asidan patient was examined and cytoplasmic inclusions and (GGCCUG)n repeat RNA foci were detected. Methods: Hematoxylin and eosin staining, immunohistochemical staining, as well as fluorescence in situ hybridization were used to investigate the cytoplasmic inclusions of ubiquitin and p62 and the (GGCCUG)n repeat RNA foci. Results: The present study showed both ubiquitin- and p62-positive inclusions in the cytoplasm of the inferior olivary nucleus of the Asidan patient, (GGCCUG)n RNA foci in neuronal nuclei of the cerebrum, cerebellum, inferior olive, spinal cord and temporal muscle, and three types of RNA foci, i.e. single small, multiple small and giant. Of interest is that the giant RNA foci, nearly 10 μm in diameter, that were detected in Purkinje cells, spinal motor neurons and most frequently in the inferior olivary nucleus, may be responsible for pivotal clinical symptoms of Asidan. Conclusions: The present study is the first report to show neuronal cytoplasmic inclusion bodies and giant RNA foci in an Asidan patient. The relationships between the giant RNA foci and neurodegeneration have yet to be studied.

Original languageEnglish
Pages (from-to)1377-1386
Number of pages10
JournalEuropean Journal of Neurology
Volume21
Issue number11
DOIs
Publication statusPublished - Nov 1 2014

Fingerprint

Spinocerebellar Ataxias
RNA
Inclusion Bodies
Olivary Nucleus
Ubiquitin
Temporal Muscle
Staining and Labeling
Purkinje Cells
Cerebrum
Motor Neurons
Hematoxylin
Eosine Yellowish-(YS)
Fluorescence In Situ Hybridization
Neurodegenerative Diseases
Introns
Cerebellum
Autopsy
Spinal Cord
Cytoplasm

Keywords

  • Asidan
  • Hexanucleotide GGCCUG expansion
  • RNA foci
  • Spinocerebellar ataxia

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Medicine(all)

Cite this

Characteristic RNA foci of the abnormal hexanucleotide GGCCUG repeat expansion in spinocerebellar ataxia type 36 (Asidan). / Liu, W.; Ikeda, Y.; Hishikawa, Nozomi; Yamashita, Toru; Deguchi, K.; Abe, Koji.

In: European Journal of Neurology, Vol. 21, No. 11, 01.11.2014, p. 1377-1386.

Research output: Contribution to journalArticle

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N2 - Background and purpose: Spinocerebellar ataxia type 36 (SCA36), also called Asidan, is an autosomal-dominant neurodegenerative disorder identified as a hexanucleotide GGCCTG repeat expansion in the first intron 1 of the NOP56 gene. In the present study, for the first time an autopsy sample from an Asidan patient was examined and cytoplasmic inclusions and (GGCCUG)n repeat RNA foci were detected. Methods: Hematoxylin and eosin staining, immunohistochemical staining, as well as fluorescence in situ hybridization were used to investigate the cytoplasmic inclusions of ubiquitin and p62 and the (GGCCUG)n repeat RNA foci. Results: The present study showed both ubiquitin- and p62-positive inclusions in the cytoplasm of the inferior olivary nucleus of the Asidan patient, (GGCCUG)n RNA foci in neuronal nuclei of the cerebrum, cerebellum, inferior olive, spinal cord and temporal muscle, and three types of RNA foci, i.e. single small, multiple small and giant. Of interest is that the giant RNA foci, nearly 10 μm in diameter, that were detected in Purkinje cells, spinal motor neurons and most frequently in the inferior olivary nucleus, may be responsible for pivotal clinical symptoms of Asidan. Conclusions: The present study is the first report to show neuronal cytoplasmic inclusion bodies and giant RNA foci in an Asidan patient. The relationships between the giant RNA foci and neurodegeneration have yet to be studied.

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