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Prevalence of repeat expansions causing autosomal dominant spinocerebellar ataxias in Hokkaido, the northernmost island of Japan

Journal of Human Genetics volume 69, pages 27–31 (2024)Cite this article

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Abstract

In Japan, approximately 30% of spinocerebellar degeneration (SCD) is hereditary, and more than 90% of hereditary SCD is autosomal dominant SCD (AD-SCD). We have previously reported the types of AD-SCD in Hokkaido, twice. In this study, we investigated the status of AD-SCD mainly due to repeat expansions, covering the period since the last report. We performed genetic analysis for 312 patients with a clinical diagnosis of SCD, except for multiple system atrophy at medical institutions in Hokkaido between January 2007 and December 2020. The median age at the time of analysis was 58 (1–86) years. Pathogenic variants causing AD-SCD due to repeat expansion were found in 61.5% (192 cases). Spinocerebellar ataxia (SCA) 6 was the most common type in 25.3% (79 cases), followed by Machado-Joseph disease (MJD)/SCA3 in 13.8% (43), SCA1 in 6.4% (20), SCA2 in 5.1% (16), SCA31 in 4.8% (15), dentatorubral-pallidoluysian atrophy in 4.8% (15), SCA7 in 0.6% (2), and SCA8 in 0.6% (2). SCA17, 27B, 36, and 37 were not found. Compared to previous reports, this study found a higher prevalence of SCA6 and a lower prevalence of MJD/SCA3. An increasing number of cases identified by genetic testing, including cases with no apparent family history, accurately revealed the distribution of disease types in Hokkaido.

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Acknowledgements

We thank all patients for their cooperation. We thank Rie Nomachi for data processing. We would like to thank the neurologists of the Department of Neurology, Hokkaido University for their attentive care of the patients during the period of this study.

Funding

This work was supported by the Japan Agency for Medical Research and Development (AMED) under grant numbers JP23ek0109527h0003 (IY), JP23ek0109674, JP23ek0109549, JP23ek0109617, JP23ek0109648 (NM); JSPS KAKENHI under grant numbers JP23H02829 (S.Miyatake); the Takeda Science Foundation (NM), and by a Grant from the Research Committee on the Medical Basis of Motor Ataxias, Health and Labor Sciences Research Grants, The Ministry of Health, Labor and Welfare, Japan under grant numbers 23FC1010 (to IY).

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Author notes

  1. These authors contributed equally: Keiichi Mizushima, Yuka Shibata.

Authors and Affiliations

  1. Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan

    Keiichi Mizushima, Shinichi Shirai, Masaaki Matsushima, Ikuko Iwata, Hiroaki Yaguchi & Ichiro Yabe

  2. Division of Clinical Genetics, Hokkaido University Hospital, Sapporo, Japan

    Yuka Shibata, Masaaki Matsushima & Ichiro Yabe

  3. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Satoko Miyatake & Naomichi Matsumoto

  4. Department of Clinical Genetics, Yokohama City University Hospital, Yokohama, 236-0004, Japan

    Satoko Miyatake

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  1. Keiichi Mizushima
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Contributions

KM, YS, SS, MM, II, HY and IY contributed to the conception and design of the study. KM, YS, SS, MM, SM, II, HY, NM and IY contributed to the acquisition and analysis of data. KM, YS, SS, MM, SM, II, HY, NM and IY contributed to drafting the text or preparing the figures.

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Correspondence to Ichiro Yabe.

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Mizushima, K., Shibata, Y., Shirai, S. et al. Prevalence of repeat expansions causing autosomal dominant spinocerebellar ataxias in Hokkaido, the northernmost island of Japan. J Hum Genet 69, 27–31 (2024). https://doi.org/10.1038/s10038-023-01200-x

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