A novel Lys141Thr mutation in small heat shock protein 22 (HSPB8) gene in Charcot-Marie-Tooth disease type 2L

Neuromuscul Disord. 2013 Aug;23(8):656-63. doi: 10.1016/j.nmd.2013.05.009. Epub 2013 Jun 21.


Charcot-Marie-Tooth disease (CMT) is a group of clinically and genetically heterogeneous peripheral neuropathies. HSPB8 gene encodes heat shock protein 22 (HSP22) which belongs to the superfamily of small stress induced proteins. Mutations in HSPB8 are implicated to CMT2L and distal hereditary motor neuropathy 2A (dHMN2A). All three reported HSPB8 mutations are interestingly located in the Lys141 residue. In the present study, we examined a Korean axonal CMT patient who presented distal limb atrophy, sensory loss, areflexia, and axonal loss of large myelinated fibers. Whole exome sequencing identified a novel missense mutation c.422A>C (p.Lys141Thr) in HSPB8 as the underlying cause of the CMT2 patient. The mutation was regarded as a de novo case because both unaffected parents have no such mutation. The patient with HSPB8 mutation is the first case in Koreans. Clinical heterogeneities have been revealed in patients with Lys141 mutation; the present patient revealed similar phenotype of CMT2L. In addition, the lower limb MRI revealed a similarity between our HSPB8 and HSPB1 patients. It seems that the Lys141 site in the alpha-crystallin domain of HSPB8 is regarded as a mutational hot spot for peripheral neuropathy development, and mutations even in the same codon can exhibit different CMT phenotypes.

Keywords: CMT2L; Charcot–Marie–Tooth disease; Exome; HSP22; HSPB8; Korean.

Publication types

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

MeSH terms

  • Adult
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / pathology
  • Charcot-Marie-Tooth Disease / physiopathology
  • DNA Mutational Analysis
  • Heat-Shock Proteins / genetics*
  • Humans
  • Lysine / genetics*
  • Magnetic Resonance Imaging
  • Male
  • Median Nerve / physiopathology
  • Muscle, Skeletal / pathology
  • Mutation / genetics*
  • Neural Conduction / genetics
  • Republic of Korea
  • Sural Nerve / pathology
  • Sural Nerve / ultrastructure
  • Threonine / genetics*


  • Heat-Shock Proteins
  • Threonine
  • Lysine

Supplementary concepts

  • Charcot-Marie-Tooth disease, Type 2I