title: Correlation between PMP-22 messenger RNA expression and phenotype in hereditary neuropathy with liability to pressure palsies.
abstract: Hereditary neuropathy with liability to pressure palsies (HNPP) is associated with a deletion in chromosome 17p11.2, which includes the gene for the peripheral myelin protein 22 (PMP-22). A "gene dosage" effect is probably the mechanism underlying HNPP, but the amount of PMP-22 mRNA in sural nerves of HNPP patients is highly variable and the role of PMP-22 underexpression in impairing myelination has yet to be clarified. We have studied 6 genetically proven HNPP patients, to evaluate the relationship between PMP-22 mRNA levels, and clinical, neurophysiological, and neuropathological findings. Underexpression of PMP-22 mRNA correlates with disease severity and with mean axon diameter and g ratio, but not with myelin thickness, number of "tomacula," or nerve conduction parameters. Our findings further confirm that underexpression of PMP-22 is the main pathogenetic mechanism underlying the severity of clinical symptoms and signs in HNPP. Smaller axons in sural nerves of HNPP patients with lower PMP-22 levels suggests that underexpression of PMP-22 may also affect axon development.
authors.affiliation: Department of Neurological Sciences and Rehabilitation, University of Genova, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Schenone
authors.forename: L
authors.initials: L
authors.lastname: Nobbio
authors.forename: C
authors.initials: C
authors.lastname: Caponnetto
authors.forename: M
authors.initials: M
authors.lastname: Abbruzzese
authors.forename: P
authors.initials: P
authors.lastname: Mandich
authors.forename: E
authors.initials: E
authors.lastname: Bellone
authors.forename: F
authors.initials: F
authors.lastname: Ajmar
authors.forename: G
authors.initials: G
authors.lastname: Gherardi
authors.forename: A J
authors.initials: AJ
authors.lastname: Windebank
authors.forename: G
authors.initials: G
authors.lastname: Mancardi
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D015536:Down-Regulation; D006801:Humans; D009185:Myelin Proteins / Q000096:biosynthesis*; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis*; D012194:RNA-Directed DNA Polymerase; D012720:Severity of Illness Index; D013497:Sural Nerve / Q000378:metabolism
chemical_list: D009185:Myelin Proteins; C073687:PMP22 protein, human; D012333:RNA, Messenger; D012194:RNA-Directed DNA Polymerase