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Mutational and clinical spectrum of centronuclear myopathy in 9 cases and a literature review of Chinese patients

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Abstract

Centronuclear myopathy (CNM) is a group of congenital myopathies with the histopathological findings of centralized nuclei in muscle fibres. In this study, we summarized the mutational spectrum and phenotypic features of nine Chinese patients with CNM and reanalysed the existing data on 32 CNM patients reported in China. In a cohort comprising nine patients, 14 variants were found in three CNM-related genes, including DNM2, RYR1, and TTN, in 4, 3, and 2 patients, respectively. Of the total 14 variants identified, nine were reported, and 5 were novel including one pathogenic, one likely pathogenic, and 3 of undetermined significance (VUS). Pathologically, we identified the percentage of muscle fibres with central nuclei was much higher in the DNM2-related CNM patients than that in other genetic type of CNM. Of the 32 genetic-diagnosed CNM patients previously reported from China, DNM2, MTM1, SPEG, RYR1, and MYH7 mutations accounted for 59.4%, 25.0%, 9.4%, 3.1%, and 3.1%, respectively. Notably, all of the 20 variants of DNM2 were missense mutations, and the missense mutations in exon 8 were found in 60.0% of DNM2 variants. The c.1106G > A/ p.R369Q (NM_001005360) occurred in 26.3% patients of this Chinese cohort with DNM2-CNM. In conclusion, CNM showed a highly variable genetic spectrum, with DNM2 as the most common causative gene in Chinese CNM patients.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Code availability

The software and code in this study are available from the corresponding author upon request.

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Acknowledgements

The authors acknowledge all patients and their families for participating in this study.

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Author notes

  1. Qi Wang and Meng Yu contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Peking University First Hospital, Xishiku St 8#, Xicheng District, Beijing, 100034, China

    Qi Wang, Meng Yu, Zhiying Xie, Jing Liu, Qingqing Wang, He Lv, Wei Zhang, Yun Yuan & Zhaoxia Wang

  2. Beijing Key Laboratory of Neurovascular Disease Discovery, Beijing, 100034, China

    Yun Yuan & Zhaoxia Wang

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  1. Qi Wang
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Contributions

All authors contributed to the study conception and design. Zhaoxia Wang take full responsibility for the paper. Material preparation, data collection, and analysis were performed by Qi Wang, Meng Yu, Jing Liu, and Qingqing Wang. Zhiying Xie checked all the genetic analyses. The first draft of the manuscript was written by Qi Wang and Meng Yu, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zhaoxia Wang.

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Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Bioethics Committee of Peking University First Hospital (2021[061]).

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Informed consent was obtained from all individual participants included in the study.

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Patients signed informed consent regarding publishing their data and photographs.

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The authors declare no competing interests.

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Supplementary Information

Table S1.

The 700 genes included in the neuromuscular disease panel. (docx 30.7 kb)

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Wang, Q., Yu, M., Xie, Z. et al. Mutational and clinical spectrum of centronuclear myopathy in 9 cases and a literature review of Chinese patients. Neurol Sci 43, 2803–2811 (2022). https://doi.org/10.1007/s10072-021-05627-y

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