Mutation in the nerve-specific 5'non-coding region of Cx32 gene and absence of specific mRNA in a CMTX1 Italian family. Mutations in brief no. 195. Online.

Charcot-Marie-Tooth type I demyelinating neuropathies are genetically heterogeneous disorders (chrmosome 17,1,X). There are at least three genes on X chromosome, the more frequently involved being Cx32 in Xq13.1. Cx32 encodes for connexin-32, a gap junction protein of 283 aminoacids. We report the results of molecular studies in a CMTX1 Italian family, in which the mutation, found in the 5'-UTR, resulted in an abnormal mRNA connexin-32 expression. Mutations in PMP22 and P0 genes were also excluded in this family. Cx32 gene analysis carried out by PCR-SSCP on family members genomic DNAs, running a 321 bp fragment spanning the TATA box, the trasciptional start site, and the non coding exon 1b, revealed a shift correlated with a transition from C to T at position 40 of exon 1b of the 12 affected members, while was not found in the controls. Then the RT PCR-SSCP on cDNA from two peripheral nerve biopsies of two heterozygous females of the family were sequenced showing only the wild-type alleles and suggesting that mutated mRNAs were too unstable to be detected. The result also suggests a regulating role of the 5'-UTR of Cx32 mRNA.