Pathogenesis of Charcot-Marie-Tooth IA (CMTIA) neuropathy

The hereditary neuropathy Charcot-Marie-Tooth (CMT) type I A is, in the majority of cases, caused by duplication of the gene for the peripheral myelin protein PMP22, which leads to abnormally increased PMP22 expression. Recent in vitro and in vivo data indicate a novel function of PMP22 in Schwann-cell growth and differentiation other than its role in myelination, and suggest that over-production of PMP22 leads to a new Schwann-cell phenotype in CMTIA. Taking these data into account, we developed a new hypothesis on the pathogenesis of CMTIA neuropathy: that the defective myelin stability and turnover observed in the disease is caused by altered PMP22 gene dosage and its resultant effect on abnormal Schwann-cell growth and differentiation.