Clinical features of SCA36: a novel spinocerebellar ataxia with motor neuron involvement (Asidan).

Yoshio Ikeda, Yasuyuki Ohta, Hatasu Kobayashi, Miyuki Okamoto, Kazuhiro Takamatsu, Taisei Ota, Yasuhiro Manabe, Koichi Okamoto, Akio Koizumi, Koji Abe

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Abstract

To characterize the phenotype of spinocerebellar ataxia type 36 (SCA36), a novel dominant disorder (nicknamed "Asidan") caused by a hexanucleotide GGCCTG repeat expansion in intron 1 of the NOP56 gene. We investigated the clinical, genetic, and neuropathologic characteristics of 18 patients with SCA36. We performed histologic evaluation of a muscle biopsy specimen from 1 patient with SCA36, and neuropathologic evaluation of an autopsied brain from another patient with SCA36. The (GGCCTG)n expansion was found in 18 ataxic patients from 9 families. The age at onset of ataxia was 53.1 ± 3.4 years, with the most frequent symptoms being truncal ataxia (100% of patients), ataxic dysarthria (100%), limb ataxia (93%), and hyperreflexia (79%). Tongue fasciculation and subsequent atrophy were found in 71% of cases, particularly in those of long duration. Skeletal muscle fasciculation and atrophy of the limbs and trunk were found in 57% of cases. Lower motor involvement was confirmed by EMG and muscle biopsy. The neuropathologic study revealed significant cerebellar Purkinje cell degeneration with obvious loss of lower motor neurons. Immunohistochemical analysis showed that NOP56 was localized to the nuclei of various neurons. Cytoplasmic or intranuclear inclusion staining of NOP56, TDP-43, and ataxin-2 was not observed in the remaining neurons. This is the first description of the unique clinical features of SCA36, a relatively pure cerebellar ataxia with progressive motor neuron involvement. Thus, SCA36 is a disease that stands at the crossroads of SCA and motor neuron disease.

Original languageEnglish
Pages (from-to)333-341
Number of pages9
JournalNeurology
Volume79
Issue number4
DOIs
Publication statusPublished - Jul 24 2012

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Spinocerebellar Ataxias
Motor Neurons
Ataxia
Fasciculation
Biopsy
Neurons
Intranuclear Inclusion Bodies
Dysarthria
Muscles
Abnormal Reflexes
Cerebellar Ataxia
Motor Neuron Disease
Muscular Atrophy
Purkinje Cells
Inclusion Bodies
Age of Onset
Introns
Atrophy
Neuron
Extremities

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Clinical features of SCA36 : a novel spinocerebellar ataxia with motor neuron involvement (Asidan). / Ikeda, Yoshio; Ohta, Yasuyuki; Kobayashi, Hatasu; Okamoto, Miyuki; Takamatsu, Kazuhiro; Ota, Taisei; Manabe, Yasuhiro; Okamoto, Koichi; Koizumi, Akio; Abe, Koji.

In: Neurology, Vol. 79, No. 4, 24.07.2012, p. 333-341.

Research output: Contribution to journalArticle

Ikeda, Y, Ohta, Y, Kobayashi, H, Okamoto, M, Takamatsu, K, Ota, T, Manabe, Y, Okamoto, K, Koizumi, A & Abe, K 2012, 'Clinical features of SCA36: a novel spinocerebellar ataxia with motor neuron involvement (Asidan).', Neurology, vol. 79, no. 4, pp. 333-341. https://doi.org/10.1212/WNL.0b013e318260436f
Ikeda, Yoshio ; Ohta, Yasuyuki ; Kobayashi, Hatasu ; Okamoto, Miyuki ; Takamatsu, Kazuhiro ; Ota, Taisei ; Manabe, Yasuhiro ; Okamoto, Koichi ; Koizumi, Akio ; Abe, Koji. / Clinical features of SCA36 : a novel spinocerebellar ataxia with motor neuron involvement (Asidan). In: Neurology. 2012 ; Vol. 79, No. 4. pp. 333-341.
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