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RFC1 repeat expansion in Japanese patients with late-onset cerebellar ataxia

Journal of Human Genetics volume 65, pages 1143–1147 (2020)Cite this article

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Abstract

Recently, the expansion of an intronic AAGGG repeat in the replication factor C subunit 1 (RFC1) gene was reported to cause cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). In Europeans, the expansion accounted for 22% of sporadic patients with late-onset ataxia. We genotyped 37 Japanese patients comprising 25 familial (autosomal recessive or undecided transmission) and 12 sporadic ones with late-onset ataxia. We found intronic repeat expansions in RFC1 in three (12%) of the familial patients and one (8.5%) of the sporadic ones. Although our cohort study was small, the disease frequency in Japanese patients with CANVAS might be lower than that in European ones. In addition, we found biallelic ACAGG repeat expansion in one patient, indicating ACAGG repeat expansion might cause CANVAS. Clinically, we found one patient with sleep apnea syndrome, which has not been reported previously. Thus, this study might expand the clinical and genetic spectrum of CANVAS.

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Acknowledgements

We thank all the participants in the present study. We also thank Prof. Jianglin Fan, Department of Molecular Pathology, University of Yamanashi, for his support in the genetic analysis in the present study. This work was supported by Grants-in-Aid from the Research Committee for Ataxic Disease (YT), the Ministry of Health, Labor and Welfare, Japan, JP18K07495 (YT) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan, and grants for AMED under Grant Numbers JP17k17772 (KK) and JP17ek0109078 (YT).

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Authors and Affiliations

  1. Department of Neurology, Graduate School of Medical Sciences, University of Yamanashi, Chuo, Yamanashi, 409-3898, Japan

    Mai Tsuchiya, Haitian Nan, Kishin Koh, Yuta Ichinose, Lihua Gao, Keisuke Shimozono, Takanori Hata & Yoshihisa Takiyama

  2. Department of Biochemistry, Graduate School of Medical Sciences, University of Yamanashi, Chuo, Yamanashi, 409-3898, Japan

    Yeon-Jeong Kim & Toshihisa Ohtsuka

  3. Department of Neuromuscular Disease, UCL Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK

    Andrea Cortese

  4. Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy

    Andrea Cortese

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  1. Mai Tsuchiya
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  2. Haitian Nan
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  3. Kishin Koh
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  4. Yuta Ichinose
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  9. Toshihisa Ohtsuka
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  10. Andrea Cortese
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  11. Yoshihisa Takiyama
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Correspondence to Yoshihisa Takiyama.

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Tsuchiya, M., Nan, H., Koh, K. et al. RFC1 repeat expansion in Japanese patients with late-onset cerebellar ataxia. J Hum Genet 65, 1143–1147 (2020). https://doi.org/10.1038/s10038-020-0807-x

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