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Chédiak–Higashi syndrome presenting as a hereditary spastic paraplegia

Journal of Human Genetics volume 67, pages 119–121 (2022)Cite this article

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Abstract

Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders characterized by weakness and leg spasticity. LYST is responsible for Chédiak–Higashi syndrome (CHS), which exhibits partial oculocutaneous albinism, primary immunodeficiency, and bleeding tendency in childhood. Although neurological symptoms of CHS also appear in adulthood, a phenotype of spastic paraplegia has rarely been reported in CHS. In this study, we investigated LYST mutations in 387 HSP patients through the Japan Spastic Paraplegia Research Consortium to clarify the frequency of LYST mutations in HSP, finding six adult patients with LYST mutations in four HSP families. They exhibited intellectual disability, cerebellar ataxia, neuropathy, and pyramidal signs. Meanwhile, only 15 patients with CHS in childhood have been revealed in a decade by a nationwide survey in Japan. Thus, LYST mutations might indicate a HSP phenotype in a considerable number of adult patients with CHS.

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Acknowledgements

The following programs provided financial support to this research, including the study design, collection, analysis, and interpretation of data, and writing of the manuscript: Grants-in-Aid from the Research Committee for Ataxic Disease (YT), the Ministry of Health, Labor and Welfare, Japan, and JSPS KAKENHI Grant Numbers 17 K17772 (KK), 19 K16910 (KK), JP18K07495 (YT), and 21K07456 (YT) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

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Authors and Affiliations

  1. Department of Neurology, Graduate School of Medical Sciences, University of Yamanashi, Yamanashi, Japan

    Kishin Koh, Mai Tsuchiya & Yoshihisa Takiyama

  2. Department of Neurology, The University of Tokyo, Tokyo, Japan

    Hiroyuki Ishiura

  3. Faculty of Health & Medical Care, Saitama Medical University, Saitama, Japan

    Haruo Shimazaki

  4. Department of Neurology, Saitama Medical University Hospital, Saitama, Japan

    Haruo Shimazaki

  5. Department of Neurology, Kyoto Takeda Hospital, Kyoto, Japan

    Takeshi Nakamura

  6. Division of Neurology, Department of Internal Medicine, Saga University Faculty of Medicine, Saga, Japan

    Hideo Hara & Kohei Suzuyama

  7. Department of Neurology, Kitano Hospital Medical Research Institute, The Tazuke-Kofukai, Osaka, Japan

    Makio Takahashi

  8. Department of Molecular Neurology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Shoji Tsuji

  9. Institute of Medical Genomics, International University of Health and Welfare, Chiba, Japan

    Shoji Tsuji

Authors
  1. Kishin Koh
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  2. Mai Tsuchiya
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  3. Hiroyuki Ishiura
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  4. Haruo Shimazaki
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  5. Takeshi Nakamura
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  6. Hideo Hara
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  7. Kohei Suzuyama
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  8. Makio Takahashi
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  9. Shoji Tsuji
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  10. Yoshihisa Takiyama
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Consortia

Japan Spastic Paraplegia Research Consortium

Contributions

KK and YT designed and organized the study. HS, TN, HH, KS, and Makio T obtained the clinical findings and genome DNA samples of the patients through JASPAC. KK, Mai T, and HI analysed LYST mutations. KK wrote the manuscript, which was edited by HI, ST, and YT.

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Correspondence to Yoshihisa Takiyama.

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Koh, K., Tsuchiya, M., Ishiura, H. et al. Chédiak–Higashi syndrome presenting as a hereditary spastic paraplegia. J Hum Genet 67, 119–121 (2022). https://doi.org/10.1038/s10038-021-00977-z

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  • DOI: https://doi.org/10.1038/s10038-021-00977-z

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