Charcot-Marie-Tooth gonosomal dominant type (CMTX1) - First findings of mutations in the gene for connexin 32 in the Czech Republic
Abstract
Charcot-Marie-Tooth disease (CMT) can be inherited either in an autosomal dominant way or recessively linked to the X chromosome. X chromosome dominant Charcot-Marie-Tooth (CMTX) is a motor sensory neuropathy which affects men more and earlier than women and men have as a rule a lower rate of conduction in the peripheral nerve, and in the pedigree the affection is never transmitted from father to son.
In a great majority of families with CMTX there are mutations in the gene for the gap junction protein connexin 32 (Cx32). The authors selected six families with demyelination type of CMT disease where neither duplication in the chromosomal area 17p11.2-12 nor transfer from male to male in the family was proved.
By direct examination the authors investigated the whole coding area of the Cx gene In a total of 29 subjects. In five families, in a total of 19 subjects, mutations of the missense type were detected, which segregate with the affection in the family.
All three detected mutations were described already in the past in patients with CMTX. These results confirm the high frequency of mutations in the Cx32 gene among CMT 1 patients with a reduced rate of conduction in the peripheral nerve, where duplication in the area 17p11.2-12 was found.
The authors draw attention to the importance and frequent incidence of X linked dominant heredity in CMT. This is the first communication on confirmed CMTX families in the Czech Republic.