title: A novel mutation of myelin protein zero associated with an axonal form of Charcot-Marie-Tooth disease.
abstract: OBJECTIVE
  To report a new mutation in the MPZ gene which encodes myelin protein zero (P0), associated with an axonal form of Charcot-Marie-Tooth disease (CMT).
  
  
  METHODS
  Three patients from an Italian family with a mild, late onset axonal peripheral neuropathy are described clinically and electrophysiologically. To detect point mutation in MPZ gene the whole coding sequence was examined. The structure of the mutated protein was investigated using the three dimensional model of P0.
  
  
  RESULTS
  All patients showed a relatively mild CMT phenotype characterised by late onset and heterogeneity of the clinical and electrophysiological features. Molecular analysis demonstrated a novel heterozygous T/A transversion in the exon 3 of MPZ gene that predicts an Asp109Glu amino acid substitution in the extracellular domain of the P0. Asp109 is found at the protein surface, on beta strand E, in the interior of the P0 tetramer.
  
  
  CONCLUSIONS
  The identification of Asp109Glu mutation confirms the pivotal role of P0 in axonal neuropathies and stresses the phenotypic heterogeneity associated with MPZ mutations. This study suggests the value of screening for MPZ mutations in CMT family members with minor clinical and electrophysiological signs of peripheral neuropathy.
authors.affiliation: Department of Neurological Sciences, University of Naples Federico II, Naples, Italy. lusantor@unina.it
authors.forename: L
authors.initials: L
authors.lastname: Santoro
authors.forename: F
authors.initials: F
authors.lastname: Manganelli
authors.forename: E
authors.initials: E
authors.lastname: Di Maria
authors.forename: D
authors.initials: D
authors.lastname: Bordo
authors.forename: D
authors.initials: D
authors.lastname: Cassandrini
authors.forename: F
authors.initials: F
authors.lastname: Ajmar
authors.forename: P
authors.initials: P
authors.lastname: Mandich
authors.forename: E
authors.initials: E
authors.lastname: Bellone
mesh_terms: D000368:Aged; D001369:Axons / Q000502:physiology*; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D003062:Codon; D004252:DNA Mutational Analysis; D004151:Dipeptides / Q000235:genetics; D004576:Electromyography / Q000295:instrumentation; D005091:Exons / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000503:physiopathology; D018993:Myelin P0 Protein / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*
chemical_list: D003062:Codon; D004151:Dipeptides; D018993:Myelin P0 Protein; C038676:aspartylglutamate