Late-onset CMT2 associated with a novel missense mutation in the cytoplasmic domain of the MPZ gene

Clin Neurol Neurosurg. 2010 Nov;112(9):798-800. doi: 10.1016/j.clineuro.2010.07.020. Epub 2010 Aug 25.


Phenotypic variations have been reported in Charcot-Marie-Tooth disease type 2 (CMT2) including age-at-onset, disease progression and severity. Sporadic cases with CMT2 have also been demonstrated by genetic test. We here report a patient with late-onset CMT2 without family history, who developed gait disturbance at the age of 68. Sequence analysis revealed a novel heterozygous Arg198Gly mutation in the cytoplasmic domain of the major peripheral myelin protein zero (MPZ). The mutation is located in the protein kinase C (PKC) alpha substrate motif (RSTK) of MPZ, presumably leading to the loss of PKC-mediated phosphorylation in adhesion. Routine genetic test for CMT is not recommended for every patient with late-onset peripheral neuropathy without known causes, however, the genetic test may be taken into consideration if the patient shows a clinical phenotype similar to that of CMT, and the possibility of a de novo mutation cannot be excluded.

Publication types

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

MeSH terms

  • Aged
  • Charcot-Marie-Tooth Disease / diagnosis
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / pathology
  • Cytoplasm / metabolism*
  • Electromyography
  • Electrophysiological Phenomena
  • Evoked Potentials, Somatosensory / physiology
  • Humans
  • Male
  • Motor Neurons / physiology
  • Muscle Weakness / etiology
  • Mutation, Missense / genetics*
  • Myelin P0 Protein / genetics*
  • Neural Conduction / physiology
  • Phosphorylation
  • Protein Kinase C / metabolism
  • Sural Nerve / pathology


  • Myelin P0 Protein
  • Protein Kinase C