Abstract Details

Title Cerebellar Ataxia with SYNE1 Mutation Accompanying Motor Neuron Disease

Topic Movement Disorders

Presentation(s) P05 - (-)

Poster/Presentation
Number 045

Objective

Background BACKGROUND: Autosomal recessive SCAs are a group of hereditary ataxias that are poorly understood, and most of the cases have been remained undiagnosed. This is presumably because of the rarity of the disease, and also our lacking of economical methods of sequencing numerous exons until recently. SYNE1 was identified as a cause of autosomal recessive cerebellar ataxia in French-Canadian families whose ancestors originated mostly from the same region of Quebec, Canada. Until our current report, the presence of SYNE1-related SCA outside of the French-Canadian population has been unknown.

Design/Methods DESIGN/METHODS: Among 120 patients with cerebellar ataxia visiting a neurological department in Osaka city located in western Japan, 3 patients were born from consanguineous parents. We performed exome sequencing for the 3 patients.The research procedure was approved by the Ethics Committee of Hiroshima University. All examinations were performed after obtaining informed consent from the patients or their families.

Results RESULTS: Three patients had a novel homozygous frameshift or nonsense mutation in the SYNE1 gene. Notably, the patient with harbored an additional homozygotic missense mutation. Two of the 3 patients presented slowly progressive pure cerebellar ataxia with less disabilities that were analogous to the phenotype reported in the original paper, whereas a patient with a double mutation exhibited a prominent motor neuron involvement antecedent to cerebellar ataxia.

Conclusions CONCLUSIONS: We confirm that SYNE1 mutations are a cause of autosomal recessive SCA in multiple ethnicities utilizing exome sequencing technique. Our findings also suggest that SYNE1 mutations may have potential impact toward developing motor neuron dysfunction.

Authors/Disclosures
PRESENTER	No disclosure on file
Ryosuke Miyamoto, MD	No disclosure on file
David C. Norris	No disclosure on file
	No disclosure on file
Douglas L. Arnold, MD, FAAN (Montreal Neurological Institute, McGill Univ)	Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BMS. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Frequency Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Arnold has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Shionogi. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Xfacto communications. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biohaven. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Find therapeutics. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GSK. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Idorsia. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Kiniksa. Dr. Arnold has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Clario.
	No disclosure on file
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Hideshi Kawakami	No disclosure on file

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