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PSP-Phenotype in SCA8: Case Report and Systemic Review

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Abstract

Spinocerebellar ataxia type 8 (SCA8) is a rare autosomal dominant neurodegenerative disease caused by expanded CTA/CTG repeats in the ATXN8OS gene. Many patients had pure cerebellar ataxia, while some had parkinsonism, both without causal explanation. We analyzed the ATXN8OS gene in 150 Japanese patients with ataxia and 76 patients with Parkinson’s disease or related disorders. We systematically reassessed 123 patients with SCA8, both our patients and those reported in other studies. Two patients with progressive supranuclear palsy (PSP) had mutations in the ATXN8OS gene. Systematic analyses revealed that patients with parkinsonism had significantly shorter CTA/CTG repeat expansions and older age at onset than those with predominant ataxia. We show the imaging results of patients with and without parkinsonism. We also found a significant inverse relationship between repeat sizes and age at onset in all patients, which has not been detected previously. Our results may be useful to genetic counseling, improve understanding of the pathomechanism, and extend the clinical phenotype of SCA8.

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Acknowledgments

The authors thank Dr. Abe of the Department of Neurology, Okayama University, for technical assistance in the analysis of the NOP56 gene causative for SCA36.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Neurology, Faculty of Medicine, Kindai University, 377-2 Ohno-Higashi, Osaka-sayama, Osaka, 589-8511, Japan

    Makoto Samukawa, Makito Hirano, Kazumasa Saigoh, Shigeru Kawai, Yukihiro Hamada & Susumu Kusunoki

  2. Department of Neurology, Kindai University Sakai Hospital, 2-7-1 Harayamadai, Minami-ku, Sakai, Osaka, 590-0132, Japan

    Makito Hirano, Yukihiro Hamada & Yusaku Nakamura

  3. Department of Vascular Neurology, National Hospital Organization Osaka Minami Medical Center, 2-1 Kidohigashimachi, Kawachinagano, Osaka, 586-8521, Japan

    Daisuke Takahashi

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  1. Makoto Samukawa
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Contributions

1. Design or conceptualization of the study.

2. Acquisition of the data.

3. Analysis or interpretation of the data.

4. Drafting or revising the manuscript for intellectual content.

Dr. Makoto Samukawa has contributed to 1, 2, and 3.

Dr. Makito Hirano has contributed to 2, 3, and 4.

Dr. Kazumasa Saigoh has contributed to 2, 3, and 4.

Dr. Shigeru Kawai has contributed to 2, 3, and 4.

Dr. Yukihiro Hamada has contributed to 2, 3, and 4.

Dr. Daisuke Takahashi has contributed to 2, 3, and 4.

Dr. Yusaku Nakamura has contributed to 1, 3, and 4.

Dr. Susumu Kusunoki has contributed to 1, 3, and 4.

Corresponding author

Correspondence to Makito Hirano.

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Conflict of Interest

None of the authors have any conflict of interest, including financial, personal, or other relationships with other people or organizations within 3 years since beginning the work submitted that could inappropriately influence (bias) our work.

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All authors have approved the final article and consented to publish.

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Supplemental figure 1

Age at examination and repeat size in unaffected individuals with CTA/CTG repeat expansions in the ATXN8OS gene (unaffected). Patients with SCA8 (affected) were grouped according to their repeat sizes every ten repeats, and the oldest age at onset among the groups was also plotted. Only approximately 20% of unaffected individuals were older than the oldest age of patients with similar repeat sizes. (JPG 29 kb)

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Samukawa, M., Hirano, M., Saigoh, K. et al. PSP-Phenotype in SCA8: Case Report and Systemic Review. Cerebellum 18, 76–84 (2019). https://doi.org/10.1007/s12311-018-0955-0

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