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 ass ociated with a deletion in chromosome 17p11.2, which includes the gene for the peripheral myelin protein 22 (PMP-22). A ''gene dosage'' effe ct 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 clar ified. We have studied 6 genetically proven HNPP patients, to evaluate the relationship between PMP-22 mRNA levels, and clinical, neurophysi ological, and neuropathological findings, Underexpression of PMP-22 mR NA 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 underexpress ion of PMP-22 is the main pathogenetic mechanism underlying the severi ty of clinical symptoms and signs in HNPP. Smaller axons in sural nerv es of HNPP patients with lower PMP-22 levels suggests that under expre ssion of PMP-22 may also affect axon development.