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Clinical genetics of Charcot–Marie–Tooth disease

Journal of Human Genetics volume 68, pages 199–214 (2023)Cite this article

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Abstract

Recent research in the field of inherited peripheral neuropathies (IPNs) such as Charcot–Marie–Tooth (CMT) disease has helped identify the causative genes provided better understanding of the pathogenesis, and unraveled potential novel therapeutic targets. Several reports have described the epidemiology, clinical characteristics, molecular pathogenesis, and novel causative genes for CMT/IPNs in Japan. Based on the functions of the causative genes identified so far, the following molecular and cellular mechanisms are believed to be involved in the causation of CMTs/IPNs: myelin assembly, cytoskeletal structure, myelin-specific transcription factor, nuclear related, endosomal sorting and cell signaling, proteasome and protein aggregation, mitochondria-related, motor proteins and axonal transport, tRNA synthetases and RNA metabolism, and ion channel-related mechanisms. In this article, we review the epidemiology, genetic diagnosis, and clinicogenetic characteristics of CMT in Japan. In addition, we discuss the newly identified novel causative genes for CMT/IPNs in Japan, namely MME and COA7. Identification of the new causes of CMT will facilitate in-depth characterization of the underlying molecular mechanisms of CMT, leading to the establishment of therapeutic approaches such as drug development and gene therapy.

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Acknowledgements

Akihiro Hashiguchi, Masahiro Ando, Jun-Hui Yuan, Hajime Tanabe, Yusuke Sakiyama, Yu Hiramatsu, Tomonori Nakamura, Takaki Taniguchi, Yuji Okamoto, Eiji Matsuura, and Akiko Yoshimura at Kagoshima University were involved in the study design, data analysis, and data interpretation. They critically revised the report, commented on drafts of the manuscript, and approved the final report. The authors appreciate Tomoko Ohnishi and Akiko Yoshimura at Kagoshima University, for their great technical assistance. The authors are supported by Enago (www.enago.jp) for reviewing the English in this report. We appreciate the Division of Gene Research, Research Support Centre, Kagoshima University, for the use of their facilities. This work was supported by Grants-in-Aid from the Research Committee of Ataxia, Health Labour Sciences Research Grant, the Ministry of Health, Labour and Welfare, Japan (20317603, 201610002B). This research was also supported by the Research program for conquering intractable disease from Japan agency for Medical Research and development (AMED) (201442014A, 201442071A, 17929553) and JSPS KAKENHI Grant Numbers JP18H02742, JP20K16604, JP21K15702, JP21H02842.

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  1. Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

    Yujiro Higuchi & Hiroshi Takashima

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YH and HT were responsible for conception, design, and acquisition and analysis of data for this study. YH was responsible for writing the manuscript.

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Higuchi, Y., Takashima, H. Clinical genetics of Charcot–Marie–Tooth disease. J Hum Genet 68, 199–214 (2023). https://doi.org/10.1038/s10038-022-01031-2

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  • DOI: https://doi.org/10.1038/s10038-022-01031-2

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