Abstract Details

Title Clinical Features and Molecular Pathogenesis of Asidan/SCA36: A Novel Spinocerebellar Ataxia with Motor Neuron Involvement

Topic Movement Disorders

Presentation(s) P05 - (-)

Poster/Presentation
Number 049

Objective

Background BACKGROUND: Although a number of genetic loci responsible for SCAs were identified, the detailed clinical features and pathomechanisms for each SCA subtype have not been clarified.

Design/Methods DESIGN/METHODS: We investigated the clinical, genetic, and neuropathological characteristics of 18 Asidan/ SCA36 patients. We performed histological evaluation of a muscle biopsy specimen from 1 Asidan/ SCA36 patient, and neuropathological evaluation and expression studies of NOP56 and related genes using an autopsied brain from another Asidan/ SCA36 patient.

Results RESULTS: 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 electromyography and muscle biopsy. The neuropathological 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. Ribonuclear foci containing expanded GGCCUG repeats were found in Purkinje cells.

Conclusions CONCLUSIONS: The unique clinical features of Asidan/ SCA36 were revealed as a relatively pure cerebellar ataxia with progressive motor neuron involvement. Thus, Asidan/ SCA36 is a disease that stands at the crossroads of SCA and motor neuron disease.

Authors/Disclosures
PRESENTER	No disclosure on file
Alex Rovira	Alex Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofy. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers. Alex Rovira has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer. Alex Rovira has stock in Tensor Medical.
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Kazuhiro Takamatsu, MD	No disclosure on file
Taisei Ota	No disclosure on file
Yasuhiro Manabe, MD	No disclosure on file
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