Abstract
Spinocerebellar ataxia type 15 (SCA15) is an autosomal dominant neurodegenerative disorder clinically characterized by late-onset, slowly progressive pure cerebellar ataxia. This disease is caused by a heterozygous deletion of the inositol 1, 4, 5-triphosphate receptor type 1 (ITPR1) gene, suggesting that haploinsufficiency of the receptor function is the plausible disease mechanism. To clarify the prevalence of SCA15 in Japan, we designed four sets of probes and primers in different regions of ITPR1 and performed TaqMan PCR assay to search for gene deletions in 226 index SCA patients excluded for repeat expansion disorders. Deletion was found in only one patient, in whom gait ataxia started at 51 years of age and progressed to show cerebellar ataxia. This study demonstrates a simple but efficient method for screening ITPR1 deletion. We also conclude that ITPR1 gene deletions are much rare in Japan than in Europe, comprising only 0.3% in all SCAs in Japan.
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Acknowledgements
We would like to thank Mrs Hitomi Matsuo for her technical assistance.
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Dr Ishikawa received research grants from the Kobayashi Magobei Research Foundation, Mitsubishi Zaidan Research Foundation, the Grants-in-Aid for Scientific Research (21591072 and 21249054), Japan Society for the Promotion of Science, Japan, Grant-in-Aid for Scientific Research on Innovative Areas (23129503) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Health and Labour Sciences Research Grants on Human Genome, Ministry of Health, Labour and Welfare, Japan. Dr Mizusawa received research grants from the Grants-in-Aid for Scientific Research (21249054), Japan Society for the Promotion of Science, Japan, the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology of Japan, the Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Saitama, Japan, and the Health and Labour Sciences Research Grants Ataxic Diseases, Ministry of Health, Labour and Welfare, Japan.
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Obayashi, M., Ishikawa, K., Izumi, Y. et al. Prevalence of inositol 1, 4, 5-triphosphate receptor type 1 gene deletion, the mutation for spinocerebellar ataxia type 15, in Japan screened by gene dosage. J Hum Genet 57, 202–206 (2012). https://doi.org/10.1038/jhg.2012.5
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DOI: https://doi.org/10.1038/jhg.2012.5
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