The D355V mutation decreases EGR2 binding to an element within the Cx32 promoter

Mutations in the early growth response 2 (EGR2) gene are associated with so me forms of Charcot-Marie-Tooth disease (CMT) and other demyelinating neuro pathies. These mutations modify the EGR2 binding to specific DNA sequences suggesting a role in the transcriptional control of myelination-specific ge nes. Here we show that the D355V mutation, associated with a CMT case combi ning axonal and demyelinating abnormalities, reduces three times the affini ty of EGR2 to its consensus sequence and ten times its affinity to a sequen ce in the human Cx32 promoter. These findings could indicate that this EGR2 mutation leads to the development of CMT1 through the transcriptional dere gulation of Cx32 gene. (C) 2001 Academic Press.