A novel missense pathogenic variant in NEFH causing rare Charcot-Marie-Tooth neuropathy type 2CC

Abstract

The purpose of this research is to explore the underlying genes of Charcot-Marie-Tooth (CMT). Technologies such as electrophysiological testing and gene sequencing have been applied. We identified a novel variant NEFH c.2215C>T(p.P739S)(HGNC:7737) in a heterozygous state, which was considered to be pathogenic for CMT2CC(OMIM:616924).The proband and his brothers presented with muscle atrophy of hand and calf and moderately decreased conduction velocities. By whole exome sequencing analysis, we found the novel missense pathogenic variant in the proband, his brother and mother. This report broadened current knowledge about intermediate CMT and the phenotypic spectrum of defects associated with NEFH. In addition, the proband carried other five variants {HSPD1c.695C>A (p.S232X), FLNCc.1073A>G (p.N358S), GUSBc.323C>A (p.P108Q), ACY1 c.1063-1G>A and APTX c.484-2A>T}, which have not been reported until now. The NEFH c.2215C>T (p.P739S) give us a new understanding of CMT, which might provide new therapeutic targets in the future

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Funding

We thank the patients for participating in this study. This work was supported by Henan Natural Science Foundation (No. 182300410333) and Scientific and Technological Achievements Transfer and Transformation Project of Henan sub-center of SCA (No. 2018105).

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Liang Qiao and Jiannan Wu were involved in the research project (execution). Huifang Peng and Anran Liu were involved in analyzing and interpreting the data. Jiarui Huang was involved in critical revision of the manuscript. Junqiang Yan was involved in the research project (conception, design, and organization) and drafting and critical revision of the manuscript for important intellectual content (writing, review, and critique).

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Correspondence to Junqiang Yan.

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This work was approved by the medical ethics committee of the First Affiliated Hospital of Henan University of Science and Technology.

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Yan, J., Qiao, L., Peng, H. et al. A novel missense pathogenic variant in NEFH causing rare Charcot-Marie-Tooth neuropathy type 2CC. Neurol Sci (2020). https://doi.org/10.1007/s10072-020-04595-z

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Keywords

  • Charcot-Marie-Tooth;
  • NEFH;
  • CMT2CC;
  • Variant;
  • Family