Vincristine exacerbates asymptomatic Charcot-Marie-tooth disease with a novel EGR2 mutation

Neurogenetics. 2012 Feb;13(1):77-82. doi: 10.1007/s10048-012-0313-1. Epub 2012 Jan 25.


Neurotoxicity is a common side effect of vincristine (VCR) treatment. Severe exacerbations of neuropathy have been reported in patients with Charcot-Marie-tooth disease (CMT) 1A with duplication of the peripheral myelin protein 22 (PMP22) gene. However, whether or not VCR exacerbates neuropathies through mutations in other CMT-associated genes besides PMP22 duplication has not been well studied. The purpose of this study was to identify mutations in any CMT-associated genes in a patient with hypersensitivity to VCR. We performed clinical, electrophysiological, and genetic examinations of a 23-year-old woman, who was hypersensitive to low-dose VCR, and her healthy mother. DNA analysis was performed using our specially designed resequencing array that simultaneously screens for 28 CMT-associated genes. Electrophysiological studies revealed that the patient and her healthy mother had demyelinating polyneuropathy. Furthermore, they showed the same novel mutation in the early growth response 2 (EGR2) gene. Recognizing pre-existing asymptomatic CMT by electrophysiological studies and genetic analysis before VCR treatment allowed us to prevent severe VCR-induced neuropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / pathology*
  • Charcot-Marie-Tooth Disease / physiopathology*
  • DNA Mutational Analysis
  • Early Growth Response Protein 2 / genetics*
  • Female
  • Hereditary Sensory and Motor Neuropathy / chemically induced*
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Neural Conduction / drug effects
  • Neural Conduction / physiology
  • Sequence Alignment
  • Vincristine / adverse effects*
  • Young Adult


  • Antineoplastic Agents, Phytogenic
  • EGR2 protein, human
  • Early Growth Response Protein 2
  • Vincristine