Mutation of the myelin P0 gene in Charcot-Marie-tooth neuropathy type 1

We had previously reported that the myelin P0 gene was responsible for Charcot-Marie-Tooth neuropathy type 1B (CMT1B). In this study we found a different mutation of the P0 gene in a family of Charcot-Marie-Tooth neuropathy type 1 without a DNA duplication in chromosome 17p11.2. The mutation, a histidine substitution for arginine at amino acid position 98, is located in the extracellular domain of P0 like as the mutations in the three pedigrees with CMT1B. The extracellular domain forms an immunoglobulin domain responsible for the function of P0 as an adhesion molecule. Alterations in the tertiary structure of the extracellular domain of P0 would modify the function of P0, resulting in an impairment of peripheral myelin compaction.