[Molecular pathology of Charcot-Marie-Tooth disease type 1A: abnormal expression of PMP-22]

In the majority of Charcot-Marie-Tooth disease type 1A (CMT1A) patients, the peripheral myelin protein 22 (PMP-22) gene maps within 1.5 megabase duplication on chromosome 17p11.2-12. The PMP-22 gene dosage is believed to be a major determining factor in the molecular pathology of CMT1A. Median nerve conduction velocities were below 35 m/sec in 17 CMT1A patients examined. Northern blot analysis showed that the mean relative ratio of PMP-22 mRNA levels in biopsied nerves of 5 patients with CMT1A is significantly higher than that in disease controls. Immunohistochemical analysis demonstrated that Schwann cell cytoplasm including onion bulbs as well as the myelin sheath was positive for PMP-22 in some patients with CMT1A, while PMP-22 was expressed only on compact portion of the myelin sheath in non-CMT1A patients and normal subjects. A minority of CMT1A are known to carry dominant and recessive point mutations in PMP-22. Some patients with Dejerine-Sottas syndrome (DSS) also have dominant and recessive point mutations in PMP-22. Instead of being two completely distinct disease entities, DSS and CMT1A form a spectrum of inherited PMP-22 related neuropathies, including hereditary neuropathy with liability to pressure palsies which carries a deletion of the PMP-22 gene.