Frontiers in Neurology (Dec 2020)

Genetic and Clinical Features in 24 Chinese Distal Hereditary Motor Neuropathy Families

  • Yongzhi Xie,
  • Zhiqiang Lin,
  • Pukar Singh Pakhrin,
  • Xiaobo Li,
  • Binghao Wang,
  • Lei Liu,
  • Shunxiang Huang,
  • Huadong Zhao,
  • Wanqian Cao,
  • Zhengmao Hu,
  • Jifeng Guo,
  • Lu Shen,
  • Beisha Tang,
  • Ruxu Zhang

DOI
https://doi.org/10.3389/fneur.2020.603003
Journal volume & issue
Vol. 11

Abstract

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Background and Objectives: Distal hereditary motor neuropathy (dHMN) is a clinically and genetically heterogeneous group of inherited neuropathies. The objectives of this study were to report the clinical and genetic features of dHMN patients in a Chinese cohort.Aims and Methods: We performed clinical assessments and whole-exome sequencing in 24 dHMN families from Mainland China. We conducted a retrospective analysis of the data and investigated the frequency and clinical features of patients with a confirmed mutation.Results: Two novel heterozygous mutations in GARS, c.373G>C (p.E125Q) and c.1015G>A (p.G339R), were identified and corresponded to the typical dHMN-V phenotype. Together with families with WARS, SORD, SIGMAR1, and HSPB1 mutations, 29.2% of families (7/24) acquired a definite genetic diagnosis. One novel heterozygous variant of uncertain significance, c.1834G>A (p.G612S) in LRSAM1, was identified in a patient with mild dHMN phenotype.Conclusion: Our study expanded the mutation spectrum of GARS mutations and added evidence that GARS mutations are associated with both axonal Charcot-Marie-Tooth and dHMN phenotypes. Mutations in genes encoding aminoamide tRNA synthetase (ARS) might be a frequent cause of autosomal dominant-dHMN, and SORD mutation might account for a majority of autosomal recessive-dHMN cases. The relatively low genetic diagnosis yield indicated more causative dHMN genes need to be discovered.

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