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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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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DOI: https://doi.org/10.1038/s10038-020-0807-x
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