Abstract Details

Title Non-coding repeats in the ATXN8OS gene are expanded in Japanese patients with amyotrophic lateral sclerosis

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P3 - Poster Session 3 (5:30 PM-6:30 PM)

Poster/Presentation
Number 1-005

Objective We intended to assess the contribution of non-coding repeat expansions in Japanese patients with amyotrophic lateral sclerosis (ALS).

Background Non-coding repeat expansions in the C9ORF72 gene is frequently found in sporadic ALS in Western countries (4–21% of all sporadic ALS), but is rare in Japan (<0.5%). Spinocerebellar ataxia type 8 (SCA8) is a non-coding repeat disease caused by expanded CTA/CTG repeats in the ATXN8OS gene. Many patients had pure cerebellar ataxia, while some had parkinsonism. Several lines of evidence suggest the involvement of upper and lower motor neurons in SCA8, but a positive association between SCA8 and ALS remains to be elucidated. Spinocerebellar ataxia type 36 (SCA36) is another non-coding repeat disease caused by mutations in the NOP56 gene, and is characterized by motor neuron involvement.

Design/Methods

We analyzed the ATXN8OS, C9ORF72, and NOP56 genes in 102 Japanese patients with sporadic ALS and in 10 patients who had either sporadic or familial ALS with mutations in know ALS-genes. Clinical and radiological information was summarized in mutation-positive patients.

Results Three of the 102 patients with sporadic ALS (3%) had mutations in the ATXN8OS gene, while no patient had a mutation in the C9ORF72 or NOP56 gene. No patient had two different mutated genes. The mutation-positive patients were clinically characterized by neck weakness or bulbar-predominant symptoms. Videofluorography revealed rapidly progressive or severe dysphagia.

Conclusions Our results suggest the importance of non-coding repeat expansions in Japanese patients with ALS, and extend the clinical phenotype of SCA8. Three percent seems small, but is still relatively large for Japan, since the most commonly mutated genes, including the SOD1 and SQSTM1 genes, only account for 2-3% of sporadic patients each.

Authors/Disclosures
Makito Hirano PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Susumu Kusunoki (Kinki University School of Medicine)	No disclosure on file

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