Type 2E giant axons research from U of Verona

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Research from J Peripher Nerv Syst. 2004 Jun;9(2):124.

Are giant axons a pathological marker of charcot-marie-tooth neuropathy

type 2E?

Cavallaro T, Fabrizi G, Angiari C, Lus G, Cabrini I, Cotrufo R, Rizzuto

N.

Department of Neurological and Visual Sciences, Section of Clinical

Neurology, University of Verona.

Background: According to electrophysiological and pathological criteria

Charcot Marie Tooth (CMT) disease includes primary demyelinating forms

(CMT1) and neuropathies with primary axonal loss (CMT2). In CMT1,

genetic analysis provided some associations between characteristic

lesions and different proteins. In CMT2, four genes were identified

recently (CMT2A, B, D, E); the molecular diagnosis is complex and

phenotypical hallmarks are lacking.

Objectives: To describe the nerve biopsy in three pedigrees with CMT2E

caused by mutations of the neurofilament-light chain gene (NF-L): two

pedigrees from Campania sharing a Pro22Ser substitution in the head

domain of protein and one pedigree from Apulia with a novel Leu268Prol

substitution in the central rod domain. In all three pedigrees

electrophysiology was consistent with a mixed, demyelinating and axonal

neuropathy.

Results: The three patients analysed revealed a primary axonopathy

characterized by giant axonal swelling filled with densely packed

neurofilaments and some atrophic axons. Conclusions: We propose that, in

the diagnostic work up of CMT2, giant axons may orientate towards CMT2E.

The pathological alterations detected correlate intuitively with an

altered function of the neurofilaments which constitute the axonal

cytoskeleton and are critical for radial growth and for axonal

transport.