CLINICAL PHENOTYPES OF DIFFERENT MPZ (P-0) MUTATIONS MAY INCLUDE CHARCOT-MARIE-TOOTH TYPE 1B, DEJERINE-SOTTAS, AND CONGENITAL HYPOMYELINATION

Hereditary demyelinating peripheral neuropathies consist of a heteroge neous group of genetic disorders that includes hereditary neuropathy w ith liability to pressure palsies (HNPP), Charcot-Marie-Tooth disease (CMT), Dejerine-Sottas syndrome (DSS), and congenital hypomyelination (CH). The clinical classification of these neuropathies into discrete categories can sometimes be difficult because there can be both clinic al and pathologic variation and overlap between these disorders. We ha ve identified five novel mutations in the myelin protein zero (MPZ) ge ne, encoding the major structural protein (P-0) of peripheral nerve my elin, in patients with either CMT1B, DSS, or CH. This finding suggests that these disorders may not be distinct pathophysiologic entities, b ut rather represent a spectrum of related ''myelinopathies'' due to an underlying defect in myelination. Furthermore, we hypothesize the dif ferences in clinical severity seen with mutations in MPZ are related t o the type of mutation and its subsequent effect on protein function ( i.e., loss of function versus dominant negative).