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A review of major causative genes in congenital myopathies

Journal of Human Genetics volume 68, pages 215–225 (2023)Cite this article

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Abstract

In this review, we focus on congenital myopathies, which are a genetically heterogeneous group of hereditary muscle diseases with slow or minimal progression. They are mainly defined and classified according to pathological features, with the major subtypes being core myopathy (central core disease), nemaline myopathy, myotubular/centronuclear myopathy, and congenital fiber-type disproportion myopathy. Recent advances in molecular genetics, especially next-generation sequencing technology, have rapidly increased the number of known causative genes for congenital myopathies; however, most of the diseases related to the novel causative genes are extremely rare. There remains no cure for congenital myopathies. However, there have been recent promising findings that could inform the development of therapy for several types of congenital myopathies, including myotubular myopathy, which indicates the importance of prompt and correct diagnosis. This review discusses the major causative genes (NEB, ACTA1, ADSSL1, RYR1, SELENON, MTM1, DNM2, and TPM3) for each subtype of congenital myopathies and the relevant latest findings.

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Fig. 1: Histology of muscle biopsy samples obtained from patients with nemaline myopathy.
Fig. 2: Histology and electron microscopy of muscle biopsy samples obtained from patients with RYR1-related myopathy and SELENON-related myopathy.
Fig. 3: Histology of muscle biopsy samples obtained from patients with myotubular/centronuclear myopathy.
Fig. 4: Histology of muscle biopsy samples obtained from patients with TPM3-related myopathy. A–D

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Acknowledgements

We thank Ms. Kaoru Tatezawa, Ms. Kazu Iwasawa, Ms. Yoko Tsutsumi, and Ms. Kanae Kanna, Mr. Hisayoshi Nakamura in NCNP for their technical assistance.

Funding

This study was supported partly by Intramural Research Grant (2-5) for Neurological and Psychiatric Disorders of NCNP and AMED under Grant Number JP21ek0109490h0002.

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Authors and Affiliations

  1. Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Tokyo, Japan

    Masashi Ogasawara & Ichizo Nishino

  2. Medical Genome Center, NCNP, Kodaira, Tokyo, Japan

    Masashi Ogasawara & Ichizo Nishino

  3. Department of Pediatrics, Showa General Hospital, Kodaira, Tokyo, Japan

    Masashi Ogasawara

Authors
  1. Masashi Ogasawara
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  2. Ichizo Nishino
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Contributions

M.O. designed the study. M.O. and I.N. wrote and edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to Ichizo Nishino.

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The authors declare no competing interests.

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All patients provided informed consent for using their samples for research after the diagnosis. This study was approved by the ethical committees of the NCNP (A2019-123).

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Ogasawara, M., Nishino, I. A review of major causative genes in congenital myopathies. J Hum Genet 68, 215–225 (2023). https://doi.org/10.1038/s10038-022-01045-w

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