X-LINKED DOMINANT CHARCOT-MARIE-TOOTH NEUROPATHY (CMTX) - NEW MUTATIONS IN THE CONNEXIN32 GENE

X-linked dominant Charcot-Marie-Tooth (CMTX) neuropathy has been mappe d to the Xq13 region. Subsequently, several mutations that could accou nt for CMTX have been detected in the coding part of the connexin32 (C x32) gene, which is located within this region. In order to develop mo re specific diagnostic tools. we have begun a systematic screening of families with dominant CMTX for mutations in the coding region of the Cx32 gene, This report describes a study of ten families and different mutations segregating with the disease were detected in five of them. In addition to the previously reported Arg22stop and Arg215Trp substi tutions, three novel mutations are described, including two different missense mutations at codon Arg22 (Arg22Pro and Arg22Gly), and a nonse nse mutation at codon Trp133. The identification of new CMTX-causing m utations is a critical step for carrier detection and presymptomatic d iagnosis, and should provide essential information on the structure-fu nction relationship of Cx32 in vitro as well as in vivo.