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Novel compound heterozygous variants in the GFPT1 gene leading to rare limb-girdle congenital myasthenic syndrome with rimmed vacuoles

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Abstract

Background: Congenital myasthenic syndrome (CMS) is a heterogeneous group of rare disorders with impaired neuromuscular transmission caused by genetic defects, which is characterized by fatigable muscle weakness. Case presentation: Herein, we report a case of limb-girdle CMS (LG-CMS) in a 15-year-old Chinese girl with limb weakness and mild ptosis. The patient presented with well-defined clinical manifestations, muscle imaging, and electrophysiological features associated with CMS. On muscle biopsy, in addition to tubular aggregates identified, an extremely unusual pathological change of rimmed vacuoles in muscle fibers was observed. Whole-exome sequencing disclosed two novel heterozygous variants (c.14 T>A and c.581 T>C) in the human glutamine-fructose-6-phosphate transaminase 1 (GFPT1) gene, leading to the substitutions of phenylalanine to tyrosine (p.F5Y) and serine (p.F194S), respectively. Both variants were predicted to be likely pathogenic by SIFT, Polyphen-2, and Mutation Taster. Treatments with pyridostigmine bromide and albuterol produced a dramatic improvement. Conclusions: Collectively, molecular genetic analysis and muscle biopsy play crucial roles in the diagnosis of GFPT1-related LG-CMS with rimmed vacuoles (a rare phenotype of CMS) and have important implications for treatment decision.

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Acknowledgments

We thank Prof. Yanchen Xie and Dr. Hui Liu for their excellent work in revising and polishing this paper.

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Author notes

  1. Yanyan Ma, Ting Xiong and Guohua Lei contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Xi’an Gaoxin Hospital, Xi’an Medical College, Xi’an, 710075, China

    Yanyan Ma, Ting Xiong, Rui Yang & Zunbo Li

  2. Domestic Department of Health Management Institute, Chinese People’s Liberation Army General Hospital, Beijing, 100853, China

    Guohua Lei

  3. Department of Neurology, Tangdu Hospital, Air Force Medical University, Xi’an, 710038, China

    Jiaqi Ding & Jun Guo

  4. Department of Neurology, Chinese People’s Liberation Army General Hospital, Beijing, 100853, China

    Dingguo Shen

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  1. Yanyan Ma
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Correspondence to Zunbo Li or Jun Guo.

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Ma, Y., Xiong, T., Lei, G. et al. Novel compound heterozygous variants in the GFPT1 gene leading to rare limb-girdle congenital myasthenic syndrome with rimmed vacuoles. Neurol Sci 42, 3485–3490 (2021). https://doi.org/10.1007/s10072-020-05021-0

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