title: Normal expression of myelin protein zero with frame-shift mutation correlates with mild phenotype.
abstract: Mutations in the gene encoding for myelin protein zero (MPZ) cause inherited demyelinating peripheral neuropathies of different severity. The molecular and cellular mechanisms by which the MPZ mutations cause neuropathy are incompletely understood. We investigated MPZ, myelin basic protein, and peripheral myelin protein 22 (PMP22) protein expression levels in a nerve biopsy of a Charcot-Marie-Tooth type 1B patient heterozygous for the Val 102 frame-shift mutation. We demonstrate by quantitative immunohistochemical as well as by Western blot analyses that MPZ expression levels were not reduced in myelin membranes, a finding that is in accordance with the mild phenotype of this patient. Our data show that heterozygous 'loss-of-function' of MPZ may not necessarily lead to reduced protein levels. In conclusion, we demonstrate that careful analysis of protein expression levels in peripheral nerve tissues provides important information with respect to the understanding of the molecular basis of these neuropathies.
authors.affiliation: Department of Research, University Hospital Basel, Pharmacenter, Basel, Switzerland. asteck@uhbs.ch
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Steck
authors.forename: Beat
authors.initials: B
authors.lastname: Erne
authors.forename: Davide
authors.initials: D
authors.lastname: Pareyson
authors.forename: Angelo
authors.initials: A
authors.lastname: Sghirlanzoni
authors.forename: Franco
authors.initials: F
authors.lastname: Taroni
authors.forename: Nicole
authors.initials: N
authors.lastname: Schaeren-Wiemers
mesh_terms: D000328:Adult; D001706:Biopsy; D015153:Blotting, Western; D003711:Demyelinating Diseases / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007150:Immunohistochemistry; D018993:Myelin P0 Protein / Q000096:biosynthesis* / Q000235:genetics*; D009185:Myelin Proteins / Q000096:biosynthesis; D010375:Pedigree; D010641:Phenotype; D013497:Sural Nerve / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology
chemical_list: D018993:Myelin P0 Protein; D009185:Myelin Proteins; C073687:PMP22 protein, human