Mutations in the peripheral myelin genes and associated genes in inherited peripheral neuropathies

The peripheral myelin protein 22 gene (PMP22), the myelin protein zero gene (MPZ, P0), and the connexin 32 gene (Cx32, GJB1) code for membrane proteins expressed in Schwann cells of the peripheral nervous system (PNS). The early growth response 2 gene (EGR2) encodes a transcription factor that may control myelination in the PNS. Mutations in the respective genes, located on human chromosomes 17p11.2, 1q22-q23, Xq13.1, and 10q21.1-q22.1, are associated with several inherited peripheral neuropathies. To date, a genetic defect in one of these genes has been identified in over 1,000 unrelated patients manifesting a wide range of phenotypes, i.e., Charcot-Marie-Tooth disease type 1 (CMT1) and type 2 (CMT2), Dejerine-Sottas syndrome (DSS), hereditary neuropathy with liability to pressure palsies (HNPP), and congenital hypomyelination (CH). This large number of genetically defined patients provides an exceptional opportunity to examine the correlation between phenotype and genotype.