PMP22 messenger RNA levels in skin biopsies: testing the effectiveness of a Charcot-Marie-Tooth 1A biomarker

Brain. 2014 Jun;137(Pt 6):1614-20. doi: 10.1093/brain/awu071. Epub 2014 May 8.


Charcot-Marie-Tooth disease type 1A (CMT1A) is associated with increased gene dosage for PMP22. Therapeutic approaches are currently aiming at correcting PMP22 over-expression. It is unknown whether PMP22 can be used as a biological marker of disease progression and therapy efficacy. We performed quantitative real-time polymerase chain reaction on skin biopsies of 45 patients with CMT1A, obtained at study entry and after 24-months of treatment either with ascorbic acid or placebo. Data of a subgroup of patients were also compared with matched healthy subjects. Finally, we analysed PMP22 messenger RNA levels in sural nerve biopsies. We did not find significant differences in the levels of any known PMP22 transcripts in treated or untreated patients with CMT1A, thus confirming that ascorbic acid does not impact on the molecular features of CMT1A. Most importantly, we did not observe any correlation between PMP22 messenger RNA levels and the different clinical and electrophysiological outcome measures, underscoring the weakness of PMP22 to mirror the phenotypic variability of patients with CMT1A. We did not find increased PMP22 messenger RNA levels in skin and sural nerve biopsies of patients with CMT1A compared with relative controls. In conclusion, this study shows that ascorbic acid does not impact on PMP22 transcriptional regulation and PMP22 is not a suitable biomarker for CMT1A.

Keywords: CMT1A; PMP22; ascorbic acid; biological marker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / analysis
  • Biopsy
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / pathology
  • Female
  • Gene Expression Regulation / physiology
  • Humans
  • Male
  • Middle Aged
  • Myelin Proteins / genetics*
  • Peripheral Nervous System Diseases / genetics
  • Peripheral Nervous System Diseases / pathology
  • RNA, Messenger / genetics*
  • Real-Time Polymerase Chain Reaction / methods
  • Skin / pathology*
  • Sural Nerve / pathology*
  • Young Adult


  • Biomarkers
  • Myelin Proteins
  • PMP22 protein, human
  • RNA, Messenger