Charcot-Marie-Tooth type X: unusual phenotype of a novel CX32 mutation

X-linked Charcot-Marie-Tooth disease (CMTX), caused by mutations in the gene encoding connexin32, is the second most common form of inherited demyelinating neuropathy, next to CMT 1A, and accounts for 10-20% of all hereditary demyelinating neuropathies.

To describe clinical and electrophysiological data of an Italian family carrying a novel mutation in the Cx32 gene.

Clinical, electrophysiological, and genetic findings of three patients carrying the Ser128Leu mutation in the intracellular domain of the Cx32 gene were reported. Brain MRI studies were also performed.

In our family the disease was characterized by a moderate-to-severe polyneuropathy affecting similarly males as well females. In the proband the phenotype was quite unusual in terms of late-onset, rapidity of evolution and severity. Abnormal brain MRI in association with CNS symptoms were also observed. Both sons had also clinical evidence of CNS involvement.

The Ser128Leu mutation in the Cx-32 gene is a novel substitution, which has not been reported so far. This novel mutation could be added to the group of Cx-32 mutations with CNS phenotypes. The identification of new CMTX causing mutations is a crucial step for carrier detection and pre-symptomatic diagnosis.