PERIPHERAL MYELIN PROTEIN-22 EXPRESSION IN CHARCOT-MARIE-TOOTH DISEASE TYPE 1A SURAL NERVE BIOPSIES

Peripheral myelin protein-22 (PMP22) is expressed in myelinating Schwa nn cells and shows significant homology to murine growth arrest-specif ic gene gas3. Charcot-Marie-Tooth disease type 1a (CMT1a) is a common hereditary demyelinating neuropathy. Recently it was demonstrated that the gene for PMP22 is duplicated in CMT1a patients. A gene dosage mec hanism has been postulated to cause CMT1a. According to this hypothesi s, the increase in copy number of PMP22 gene would lead to an elevated expression of PMP22 and thereby cause the demyelinating phenotype of CMT1a. In the present communication we analyzed PMP22 mRNA and protein expression in sural nerve biopsies from CMT1a patients and normal con trols. We show that PMP22 mRNA expression in CMT1a is not uniform. We found both elevated as well as normal PMP22 mRNA levels in patients. I nterestingly, the highest PMP22 mRNA level was found in the least affe cted patient. In contrast to the mRNA levels, PMP22 was clearly reduce d in all CMT1a patients as shown by immunohistochemistry. Thus the CMT 1a phenotype may not be strictly correlated with increased PMP22 mRNA and protein expression. Possible roles of PMP22 in the pathogenesis of CMT1a are discussed. (C) 1994 Wiley-Liss, Inc.