CMT 2: An axon regeneration signature

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J Neurogenet. 2009;23(3):324-8.

An axon regeneration signature in a Charcot-Marie-Tooth disease type 2 patient.

Cavalcanti F, Kidd T, Patitucci A, Valentino P, Bono F, Nisticò R, Quattrone A.

Institute of Neurological Sciences, National Research Council, Mangone, Cosenza,

Italy.

Charcot-Marie-Tooth disease (CMT) is one of the most common inherited peripheral

neuropathies. The underlying mutations in demyelinating forms tend to affect

genes expressed in Schwann cells (CMT types 1, 3, and 4), while axonal forms of

the disease usually have their origins in genes expressed in the affected

neurons (CMT type 2).

Repeated rounds of nerve degeneration and regeneration characterize CMT2, but

evidence for regeneration has not been demonstrated at a molecular level.

Subtractive hybridization was performed on sural nerve biopsies from a patient

presenting an axonal form of CMT and an unaffected sibling, which revealed an

overexpression of genes associated with the regeneration of axons, including

PMP22, SPARC/osteonectin, CD9, CD44, EEF1A1, and gamma-actin.

These results suggest that axonal degeneration elicits a regeneration

transcriptional response in the surrounding Schwann cells. This response

contrasts with other neurodegenerative diseases, in which programmed cell death

or an inappropriate immune response are activated.

Additionally, Lamin A/C, which is mutated in CMT2B1, was overexpressed in the

patient, suggesting that CMT-causing genes may interact in a regulatory network.