An axon regeneration signature in a Charcot-Marie-Tooth disease type 2 patient

J Neurogenet. 2009;23(3):324-8. doi: 10.1080/01677060802447585.


Charcot-Marie-Tooth disease (CMT) is one of the most common inherited peripheral neuropathies. The underlying mutations in demyelinating forms tend to affect genes expressed in Schwann cells (CMT types 1, 3, and 4), while axonal forms of the disease usually have their origins in genes expressed in the affected neurons (CMT type 2). Repeated rounds of nerve degeneration and regeneration characterize CMT2, but evidence for regeneration has not been demonstrated at a molecular level. Subtractive hybridization was performed on sural nerve biopsies from a patient presenting an axonal form of CMT and an unaffected sibling, which revealed an overexpression of genes associated with the regeneration of axons, including PMP22, SPARC/osteonectin, CD9, CD44, EEF1A1, and gamma-actin. These results suggest that axonal degeneration elicits a regeneration transcriptional response in the surrounding Schwann cells. This response contrasts with other neurodegenerative diseases, in which programmed cell death or an inappropriate immune response are activated. Additionally, Lamin A/C, which is mutated in CMT2B1, was overexpressed in the patient, suggesting that CMT-causing genes may interact in a regulatory network.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / genetics
  • Axons / metabolism
  • Axons / physiology*
  • Charcot-Marie-Tooth Disease / complications*
  • Charcot-Marie-Tooth Disease / pathology*
  • Family Health
  • Gene Expression Regulation / physiology
  • Humans
  • Hyaluronan Receptors / genetics
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Myelin Proteins / genetics
  • Nerve Degeneration / etiology*
  • Nerve Regeneration / genetics
  • Nerve Regeneration / physiology*
  • Neural Conduction / genetics
  • Osteonectin / genetics
  • Peptide Elongation Factor 1 / genetics
  • Schwann Cells / metabolism
  • Signal Transduction / genetics
  • Sural Nerve / pathology
  • Tetraspanin 29 / genetics


  • Actins
  • EEF1A1 protein, human
  • Hyaluronan Receptors
  • Intercellular Signaling Peptides and Proteins
  • Myelin Proteins
  • Osteonectin
  • PMP22 protein, human
  • Peptide Elongation Factor 1
  • Tetraspanin 29