GENOTYPE PHENOTYPE CORRELATION IN AFFECTED INDIVIDUALS OF A FAMILY WITH A DELETION OF THE ENTIRE CODING SEQUENCE OF THE CONNEXIN-32 GENE/

X-linked Charcot-Marie-Tooth disease (CMTX) is a peripheral nerve diso rder that has been linked to mutations in the connexin 32 gene (Cx32). These mutations have been shown to be genetically heterogeneous, thou gh recurrences of specific mutations in apparently unrelated families have been seen. The majority of mutations have been shown to be missen se, resulting in non-conservative amino acid changes. A few mutations resulting in a premature termination of protein translation, including both nonsense mutations as well as frameshifting microdeletions, have been documented. We would like to report a deletion mutation that app ears to eliminate the entire coding sequence of the Cx32 gene, but whi ch has been shown to segregate with a clinical phenotype not unlike th at seen in individuals with a less severe alteration of the Cx32 gene. The causes at a cellular level of the CMTX phenotype are still not fu lly clear, though there has been speculation that these may involve a dominant negative effect where the mutant connexin 32 suppresses the f unction of other connexins. Studies of kindreds such as this, where in CMTX-affected males the Cx32 gene product is totally absent, will hel p us to better understand the molecular mechanisms underlying the clin ical phenotype associated with this disorder.