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Distal myopathy due to TCAP variants in four unrelated Chinese patients

neurogenetics volume 22, pages 1–10 (2021)Cite this article

Abstract

Distal myopathies are a group of clinically and genetically heterogeneous hereditary muscle disorders characterized by progressive muscular weakness starting in the distal parts of the limbs. The most common subtype of distal myopathy is GNE myopathy, a rare muscle disease with autosomal recessive inheritance. Limb-girdle muscular dystrophy 2G (LGMD2G) is a rare autosomal recessive subtype of LGMDs caused by TCAP variant. Patients with LGMD2G can present with distal myopathy and rimmed vacuoles on muscle pathology. Thus far, the most reported TCAP mutations related to LGMD2G were recessive frameshift or nonsense variants. Here, we described four Chinese patients from unrelated families with LGMD2G due to TCAP mutations. The clinical symptoms of our patients were similar to those previously reported in LGMD2G patients. Three different pathogenic TCAP variants were identified in these patients, including two frameshift variants and one intronic variant. Autophagolysosomes have been observed in one patient by electron microscopy. Our research expands the genetic spectrum of TCAP mutations in China, indicating c.165-166insG is likely the common pathogenic variant. We also provide evidences that autophagy may be involved in the pathophysiology of LGMD2G.

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Data availability

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

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Acknowledgments

We thank the patients and their families for their participation in this study.

Funding

This study was funded by the Taishan Scholars Program of Shandong Province and 20 policy supported projects of collaborative innovation and achievement transformation in universities and research institutes of Jinan (2019GXRC050).

Author information

Author notes

  1. Xiaoqing Lv and Fei Gao contributed equally to this work.

Affiliations

  1. Department of Neurology and Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China

    Xiaoqing Lv, Wei Jiang & Hongzhi Geng

  2. Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, School of Basic Medical Sciences, Shandong University, Jinan, 250012, Shandong, China

    Fei Gao

  3. Department of Neurology and Research Institute of Neuromuscular and Neurodegenerative Diseases, Qilu Hospital, Shandong University, Jinan, 250012, Shandong, China

    Tingjun Dai, Dandan Zhao, Pengfei Lin & Chuanzhu Yan

  4. Department of Neuroscience, Yale University School of Medicine, New Haven, CT, 06511, USA

    Fuchen Liu

  5. Brain Science Research Institute, Shandong University, Jinan, 250012, Shandong, China

    Chuanzhu Yan

Authors
  1. Xiaoqing Lv
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  8. Pengfei Lin
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Contributions

Xiaoqing Lv wrote the manuscript. Data analysis was performed by Xiaoqing Lv, Fei Gao, Pengfei Lin, and Chuanzhu Yan. Xiaoqing Lv and Fei Gao collected the clinical data. Dandan Zhao performed the histology and immunohistochemistry staining. Tingjun Dai, Wei Jiang, and Hongzhi Geng helped in preparing the materials. Fuchen Liu revised the manuscript.

Corresponding author

Correspondence to Pengfei Lin.

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The authors declare that they have no conflict of interest.

Ethical statements

Study protocols were approved by the ethics committee of Qilu Hospital, Shandong University (2018-152). Informed consent was obtained from all patients.

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Lv, X., Gao, F., Dai, T. et al. Distal myopathy due to TCAP variants in four unrelated Chinese patients. Neurogenetics 22, 1–10 (2021). https://doi.org/10.1007/s10048-020-00623-4

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  • DOI: https://doi.org/10.1007/s10048-020-00623-4

Keywords

  • Limb-girdle muscular dystrophy
  • LGMD2G
  • Distal myopathy
  • GNE
  • TCAP