Correlation between PMP-22 messenger RNA expression and phenotype in hereditary neuropathy with liability to pressure palsies.
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.
Schenone
A
A
Department of Neurological Sciences and Rehabilitation, University of Genova, Italy.
Nobbio
L
L
Caponnetto
C
C
Abbruzzese
M
M
Mandich
P
P
Bellone
E
E
Ajmar
F
F
Gherardi
G
G
Windebank
A J
AJ
Mancardi
G
G
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
D009185:Myelin Proteins; C073687:PMP22 protein, human; D012333:RNA, Messenger; D012194:RNA-Directed DNA Polymerase