Heterogeneous Clinical Phenotypes of dHMN Caused by Mutation in HSPB1 Gene: A Case Series

Biomolecules. 2022 Sep 27;12(10):1382. doi: 10.3390/biom12101382.


Mutations in HSPB1 are known to cause Charcot-Marie-Tooth disease type 2F (CMT2F) and distal hereditary motor neuropathy (dHMN). In this study, we presented three patients with mutation in HSPB1 who were diagnosed with dHMN. Proband 1 was a 14-year-old male with progressive bilateral lower limb weakness and walking difficulty for four years. Proband 2 was a 65-year-old male with chronic lower limb weakness and restless legs syndrome from the age of 51. Proband 3 was a 50-year-old female with progressive weakness, lower limbs atrophy from the age of 44. The nerve conduction studies (NCS) suggested axonal degeneration of the peripheral motor nerves and needle electromyography (EMG) revealed chronic neurogenic changes in probands. Open sural nerve biopsy for proband 2 and the mother of proband 1 showed mild to moderate loss of myelinated nerve fibers with some nerve fiber regeneration. A novel p.V97L in HSPB1 was identified in proband 3, the other two variants (p.P182A and p.R127W) in HSPB1 have been reported previously. The functional studies showed that expressing mutant p.V97L HSPB1 in SH-SY5Y cells displayed a decreased cell activity and increased apoptosis under stress condition. Our study expands the clinical phenotypic spectrum and etiological spectrum of HSPB1 mutation.

Keywords: CMT2F; HSPB1; dHMN; heat shock protein; restless legs syndrome.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Charcot-Marie-Tooth Disease* / pathology
  • Female
  • HSP27 Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / genetics
  • Humans
  • Male
  • Molecular Chaperones / genetics
  • Mutation
  • Neuroblastoma*
  • Phenotype


  • HSP27 Heat-Shock Proteins
  • HSPB1 protein, human
  • Heat-Shock Proteins
  • Molecular Chaperones

Grants and funding

This research was funded by the excellent personnel training plan for Shanghai Health and Family System (No. 2018YQ13, project manager: Xiaojie Zhang), Hospital-level Project of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital (ynlc201907, project manager: Xiaojie Zhang), National Natural Science Foundation of China (81870889 and 82071258, project manager: Li Cao).