SCHWANN-CELL DIFFERENTIATION IN CHARCOT-MARIE-TOOTH-DISEASE TYPE 1A (CMT1A) - NORMAL NUMBER OF MYELINATING SCHWANN-CELLS IN YOUNG CMT1A PATIENTS AND NEURAL CELL-ADHESION MOLECULE EXPRESSION IN ONION BULBS

Charcot-Marie-Tooth disease type 1A (CMT1A) is a common hereditary dem yelinating neuropathy caused by a duplication of the gene for the myel in protein PMP22, resulting in overexpression of PMP22 in young patien ts. Although genetically well defined, the pathogenesis of the heredit ary demyelinating neuropathy CMT1A is still unclear. Homology of PMP22 cDNA to the growth arrest-specific gene gas3 and experiments in vitro showing decreased proliferation in PMP22-overexpressing Schwann cells suggest a role of PMP22 in Schwann cell differentiation. Furthermore, overexpression of PMP22 in fibroblasts induces programmed cell death. In this report we applied morphometrical methods using electron micro graphs and immunohistochemistry to further characterise Schwann cells in CMT1A nerve biopsy samples from CMT1A patients. We show that the to tal number of PMP22-expressing Schwann cells, i.e. Schwann cells that are in a 1:1 relationship with axons, was not reduced in sural nerve b iopsy samples from six young CMT1A patients. We excluded non-specific secondary Schwann cell proliferation. Thus, in young CMT1A patients wi th increased PMP22 overexpression there seems to be no evidence for al tered initial Schwann cell proliferation in achieving a 1:1 relationsh ip to axons prior to the process of de-and remyelination. Further, usi ng electron microscopy we found no evidence for apoptosis of Schwann c ells in CMT1A. However, we provide additional support for an abnormal Schwann cell phenotype in CMT1A by showing the expression of neural ce ll adhesion molecule immunoreactivity in onion bulbs. Thus, the role o f PMP22 in cell growth and differentiation does not lead to an altered number of myelinating Schwann cells but to altered Schwann cell diffe rentiation in CMT1A.