Central nervous system involvement in four patients with Charcot-Marie-Tooth disease with connexin 32 extracellular mutations

In a recent issue of this Journal 1there was a report of two cases of multiple sclerosis with duplicated CMT1A. Here we present four additional patients with Charcot-Marie-Tooth disease with CNS involvement as shown by electrophysiological studies and the presence of myelin lesions in brain MRI. In our patients point mutations were identified in GJB1, a gene coding for connexin 32 (GenBank acc number 117688). We also point to the possible importance of the position (intracellular or extracellular) of the mutations in the involvement or not of the CNS. In the process of investigating a panel of patients with Charcot-Marie-Tooth disease for mutations leading to the disease, we have screened the GJB1 gene for mutations in six patients (C12, C64, C10, and C13 (all unrelated), and C2–1 and C2–2 (brothers) who did not have a CMT1A duplication and had a family history compatible with an X linked mode of transmission. GJB1 is a gene coding for connexin 32 (Cx32), a gap junction protein that is found in both the peripheral and the central nervous systems2 …