Correlation between PMP‐22 messenger mRNA 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 17p 11.2, 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.