Clinically distinct codon 69 mutations in major myelin protein zero in demyelinating neuropathies

Mutations in the major peripheral myelin protein zero (P0) gene on chromosome 1q21-q23 have been found with the hereditary demyelinating polyneuropathy Charcot-Marie-Tooth type 1B. Here, we describe 2 patients with distinct neurological characteristics, carrying different substitutions at the same codon--Arg69His and Arg69Cys. The patients were heterozygous for the mutation, which in both appeared to be de novo. Histological examination of sural nerve biopsy specimens revealed defective myelin as well as marked differences, confirming the importance of P0 in the compaction of myelin.