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Neurological Sciences

, Volume 39, Issue 12, pp 2043–2051 | Cite as

Characterization and genetic diagnosis of centronuclear myopathies in seven Chinese patients

  • Yan Zhao
  • Zhe Zhao
  • Hongrui Shen
  • Qi Bing
  • Jing Hu
Original Article
  • 64 Downloads

Abstract

Centronuclear myopathies (CNMs) are a group of clinically and genetically heterogeneous muscle disorders. Here, we report a cohort of seven CNM patients with their clinical, histological, and morphological features. In addition, using the next-generation sequencing (NGS) technique (5/7 patients), we identified small indels: intronic, exonic, and missense mutations in MTM1, DNM2, and RYR1 genes. Further genetic studies revealed skewed X-chromosome inactivation in two female patients carrying MTM1 mutations. Based on the results of genetic analysis, these seven patients were classified as (1) X-linked recessive myotubular myopathy (patients 1–3) with MTM1 mutations and mild phenotype, (2) the autosomal dominant CNM (patients 4–6) with DNM2 mutations, and (3) the autosomal recessive CNM (patient 7) with RYR1 mutations. In all patients, histological findings featured a high proportion of fibers with central nuclei. Radial arrangement of the sarcoplasmic strands was observed in DNM2-CNM and RYR1-CNM patients. Muscle magnetic resonance imaging (MRI) revealed a proximal pattern of involvement presented in both MTM1-CNM and RYR1-CNM patients. A distal pattern of involvement was present in DNM2-CNM patients. Our findings thereby identified a number of novel features that expand the reported clinicopathological phenotype of CNMs in China.

Keywords

Centronuclear myopathies Next-generation sequencing (NGS) Myotubularin (MTM1Dynamin-2 (DNM2Ryanodine receptor-1 (RYR1) Skewed X-chromosome inactivation 

Notes

Acknowledgements

We thank the patients and their family members described for their cooperation in this study, and Dr. Jian Wu from MyGenostics Inc. for his excellent technical assistance.

Compliance with ethical standards

Conflict of interests

The authors declare that they have no conflict of interest.

Supplementary material

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Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2018

Authors and Affiliations

  • Yan Zhao
    • 1
  • Zhe Zhao
    • 1
  • Hongrui Shen
    • 1
  • Qi Bing
    • 1
  • Jing Hu
    • 1
  1. 1.Department of Neuromuscular DisorderThird Hospital of Hebei Medical UniversityShijiazhuangPeople’s Republic of China

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