CHARCOT-MARIE-TOOTH NEUROPATHY TYPE-1B IS ASSOCIATED WITH MUTATIONS OF THE MYELIN-P(0) GENE

P0, a major structural protein of peripheral myelin, is a homophilic a dhesion molecule and maps to chromosome 1q22-q23, in the region of the locus for Charcot-Marie-Tooth neuropathy type 1B (CMT1B). We have inv estigated P0 as a candidate gene in two pedigrees with CMT1B and found point mutations which are completely linked with the disease (Z=5.5, theta=0). The mutations, glutamate substitution for lysine 96 or aspar tate 90, are located in the extracellular domain, which plays a signif icant role in myelin membrane adhesion. Individuals with CMT1B are het erozygous for the normal allele and the mutant allele. Our results ind icate that P0 is a gene responsible for CMT1B.