Charcot-Marie-Tooth disease

histopathological features of the peripheral myelin protein (PMP22) duplication (CMT1A) and Connexin32 mutations (CMTX1)

Stefanie Sander, Garth A. Nicholson, Robert A. Ouvrier, James G. McLeod, John D. Pollard*

*Corresponding author for this work

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

The two most common subtypes of Charcot-Marie-Tooth (CMT) disease are CMT1A and CMTX1. To determine whether these different genetic entities display different morphological phenotypes we compared sural nerve biopsies of CMT1A patients due to PMP22 duplication with biopsies of CMTX1 patients with proven Connexin32 mutations. In CMT1A nerve biopsies we found a severe reduction in myelinated fiber density, hypermyelination as well as demyelination, and a high percentage of onion bulb formations. CMTX1 nerve biopsies showed significant differences: a higher myelinated fiber density, thinner myelin sheaths, more cluster formations, and only few onion bulb formations. Teased fibers studies in CMT1A patients showed features of demyelination and/or remyelination in almost all fibers. In contrast, teased fibers of CMTX1 patients were uniformly thinly myelinated with 5-10% active axonal degeneration and 15% segmental demyelination. Median nerve motor conduction velocities were significantly faster in CMTX1 patients (31.6 ± 5.5 m/s) than in CMT1A patients (18.2 ± 6.9 m/s). The possible roles of PMP22 and Connexin32 in the pathogenesis of CMT are discussed.

Original languageEnglish
Pages (from-to)217-225
Number of pages9
JournalMuscle and Nerve
Volume21
Issue number2
DOIs
Publication statusPublished - 1998
Externally publishedYes

Keywords

  • Charcot-Marie-Tooth disease
  • Cluster formation
  • Connexin32
  • Hypermyelination
  • Hypomyelination
  • Onion bulb formation
  • Peripheral myelin protein- 22

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