ACCUMULATION OF PERIPHERAL MYELIN PROTEIN-22 IN ONION BULBS AND SCHWANN-CELLS OF BIOPSIED NERVES FROM PATIENTS WITH CHARCOT-MARIE-TOOTH DISEASE TYPE 1A

Peripheral myelin protein 22 (PMP-22) is a glycoprotein expressed in t he myelin sheath of myelinated Schwann cells. Duplication of the PMP-2 2 gene and its gene dosage effect have been postulated to be involved in the pathogenesis in the majority of individuals with Charcot-Marie- Tooth disease type IA (CMT1A). Northern blot analysis has demonstrated that the mean relative ratio of PMP-22 mRNA/beta-actin mRNA in biopsi ed nerves of patients with CMT1A is significantly higher than that in disease controls. To investigate whether the elevated expression of PM P-22 mRNA is reflected in the amount and the localization of PMP-22, w e analyzed PMP-22, myelin basic protein (MBP), protein zero (PO), and S-100 immunoreactivities in biopsied nerves from six patients with CMT 1A, five patients with other types of CMT, five patients with acquired demyelinating neuropathies, and two normal subjects. In all patients with CMT other than CMT1A and acquired demyelinating neuropathy, as we ll as in normal subjects, the myelin sheath was immunoreactive for PMP -22, MBP, and PO, while the Schwann cell cytoplasm was immunoreactive only for S-100. In five out of six patients with CMT1A, however, the P MP-22 immunoreactivity was present not only on the myelin sheath but a lso in the Schwann cell cytoplasm and onion bulbs (OBs). Although OBs are nonspecific and also seen in other inherited or acquired demyelina ting neuropathies, the PMP-22-positive OBs were seen exclusively in CM T1A. The finding suggested that the expression of PMP-22 was abnormal for its localization and probably for the amount in patients with CMT1 A carrying duplication of the PMP-22 gene.