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

[Guest guest]

Eur J Neurol. 2008 Aug 20.

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

mutation.

Mazzeo A, Di Leo R, Toscano A, Muglia M, Patitucci A, Messina C, Vita

G.

Department of Neurosciences, Psychiatry and Anaesthesiology, AOU 'G.

o', University of Messina, Messina, Italy.

Background: 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.

Aims of the study: To describe clinical and electrophysiological data

of an Italian family carrying a novel mutation in the Cx32 gene.

Patients and methods: 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.

Results: 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.

Conclusions: 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.