Rapid progression of late onset axonal CMT associated with a novel MPZ mutation

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J Neurol Neurosurg Psychiatry. 2007 Nov;78(11):1263-6.

Rapid progression of late onset axonal Charcot-Marie-Tooth disease

associated with a novel MPZ mutation in the extracellular domain.

Laurà M, Milani M, Morbin M, Moggio M, Ripolone M, Jann S, Scaioli

V, Taroni F, Pareyson D.

UO Biochimica e Genetica, Fondazione IRCCS Istituto Neurologico

Carlo Besta, Via Celoria 11, 20133 Milan, Italy.

Myelin protein zero (MPZ) is a major component of compact myelin in

peripheral nerves where it plays an essential role in myelin

formation and adhesion.

MPZ gene mutations are usually responsible for demyelinating

neuropathies, namely Charcot-Marie-Tooth (CMT) type 1B, Déjèrine-

Sottas neuropathy and congenital hypomyelinating neuropathy.

Less frequently, axonal CMT (CMT2) associated with MPZ mutations has

been described. We report six patients (one sporadic case and five

subjects from two apparently unrelated families) with a late onset,

but rapidly progressive, axonal peripheral neuropathy. In all

patients, molecular analysis demonstrated a novel heterozygous

missense mutation (208C>T) in MPZ exon 2, causing the Pro70Ser

substitution in the extracellular domain.

The diagnosis of CMT2 associated with MPZ mutations should be

considered in both sporadic and familial cases of late onset,

progressive polyneuropathy. The mechanism whereby compact myelin

protein mutations cause axonal neuropathy remains to be elucidated.