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 language | English |
|---|---|
| Pages (from-to) | 333-341 |
| Number of pages | 9 |
| Journal | Neurology |
| Volume | 79 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Jul 24 2012 |
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ASJC Scopus subject areas
- Clinical Neurology
- Arts and Humanities (miscellaneous)
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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 journal › Article
}
TY - JOUR
T1 - Clinical features of SCA36
T2 - a novel spinocerebellar ataxia with motor neuron involvement (Asidan).
AU - Ikeda, Yoshio
AU - Ohta, Yasuyuki
AU - Kobayashi, Hatasu
AU - Okamoto, Miyuki
AU - Takamatsu, Kazuhiro
AU - Ota, Taisei
AU - Manabe, Yasuhiro
AU - Okamoto, Koichi
AU - Koizumi, Akio
AU - Abe, Koji
PY - 2012/7/24
Y1 - 2012/7/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84865332523&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865332523&partnerID=8YFLogxK
U2 - 10.1212/WNL.0b013e318260436f
DO - 10.1212/WNL.0b013e318260436f
M3 - Article
C2 - 22744658
AN - SCOPUS:84865332523
VL - 79
SP - 333
EP - 341
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 4
ER -