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BAG3 p.Pro209Ser mutation identified in a Chinese family with Charcot–Marie–Tooth disease

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Abstract

Bcl2-associated athanogene 3 (BAG3) gene mutations cause dilated cardiomyopathy and myofibrillar myopathy. Recently, a novel c.625C>T (p.Pro209Ser) mutation in BAG3 was reported to cause axonal Charcot–Marie–Tooth (CMT) disease in three families. Here, we describe two patients with adult-onset and moderate CMT in a Chinese family. Nerve conduction velocity studies revealed an axonal sensorimotor neuropathy, which was supported by sural nerve biopsy. Lower limb magnetic resonance imaging (MRI) revealed fatty infiltration more severe in the soleus and deep posterior compartment muscles than in the medial gastrocnemius and anterior compartment muscles. Whole exome sequencing identified the same c.625C>T (p.Pro209Ser) mutation in BAG3, which co-segregated with the CMT disease in this family. This study further enforces the association between BAG3 gene and CMT disease, indicating that BAG3 should be considered in the genetic testing for CMT. The p.Pro209Ser mutation with different ethnic origins might be another hotspot mutation of BAG3. MRI is helpful to detect accurate extent of muscle involvement.

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Acknowledgements

The authors are thankful to all subjects for participation in this study, and grateful to Prof. Ning Sun and his team (Electron microscopy center, Henan University of Chinese medicine) for nerve pathological preparation. We are also grateful to Prof. Yun Yuan (Peking University First Hospital) for providing the picture of a normal sural nerve pathology. This study was supported by the National Natural Science Foundation of China (no. 81873727).

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Author notes

  1. Jun Fu and Mingming Ma contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Henan Provincial People’s Hospital, People’s Hospital of Henan University, No. 7, Weiwu Road, Zhengzhou, 450003, Henan, China

    Jun Fu, Mingming Ma, Jia Song, Mi Pang, Gang Li & Jiewen Zhang

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  1. Jun Fu
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  2. Mingming Ma
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  3. Jia Song
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Correspondence to Jiewen Zhang.

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We obtained written informed consent from the patients in accordance with the ethic committee of Henan Provincial People’s Hospital and in adherence to the principles of the Declaration of Helsinki.

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Fu, J., Ma, M., Song, J. et al. BAG3 p.Pro209Ser mutation identified in a Chinese family with Charcot–Marie–Tooth disease. J Neurol 267, 1080–1085 (2020). https://doi.org/10.1007/s00415-019-09680-8

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  • DOI: https://doi.org/10.1007/s00415-019-09680-8

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