title: Rapid progression of late onset axonal Charcot-Marie-Tooth disease associated with a novel MPZ mutation in the extracellular domain.
abstract: 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.
authors.affiliation: UO Biochimica e Genetica, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy.
authors.forename: Matilde
authors.initials: M
authors.lastname: Laurà
authors.forename: Micaela
authors.initials: M
authors.lastname: Milani
authors.forename: Michela
authors.initials: M
authors.lastname: Morbin
authors.forename: Maurizio
authors.initials: M
authors.lastname: Moggio
authors.forename: Michela
authors.initials: M
authors.lastname: Ripolone
authors.forename: Stefano
authors.initials: S
authors.lastname: Jann
authors.forename: Vidmer
authors.initials: V
authors.lastname: Scaioli
authors.forename: Franco
authors.initials: F
authors.lastname: Taroni
authors.forename: Davide
authors.initials: D
authors.lastname: Pareyson
mesh_terms: D000368:Aged; D001369:Axons / Q000473:pathology*; D001706:Biopsy; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis / Q000235:genetics*; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D004252:DNA Mutational Analysis; D004200:Diseases in Twins / Q000175:diagnosis / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics; D018993:Myelin P0 Protein / Q000235:genetics*; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009460:Neurologic Examination; D010641:Phenotype; D013497:Sural Nerve / Q000473:pathology
chemical_list: D018993:Myelin P0 Protein