new mutation in CMT type 2 research from Italy

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Abstract from J Neurol Neurosurg Psychiatry. 2004 Feb; 75(2): 262-265.

A novel mutation of myelin protein zero associated with an axonal form

of Charcot-Marie-Tooth disease.

Santoro L, Manganelli F, Di E, Bordo D, Cassandrini D, Ajmar F,

Mandich P, Bellone E.

Department of Neurological Sciences, University of Naples " Federico II " ,

Naples, Italy. Department of Neuroscience, Ophthalmology and Genetics,

Section of Medical Genetics, University of Genoa, Genoa, Italy.

Structural Biology Laboratory, National Cancer Research Institute,

Genoa.

OBJECTIVE: To report a new mutation in the MPZ gene which encodes myelin

protein zero (P0), associated with an axonal form of Charcot-Marie-Tooth

disease (CMT).

METHODS: Three patients from an Italian family with a mild, late onset

axonal peripheral neuropathy are described clinically and

electrophysiologically. To detect point mutation in MPZ gene the whole

coding sequence was examined. The structure of the mutated protein was

investigated using the three dimensional model of P0.

RESULTS: All patients showed a relatively mild CMT phenotype

characterised by late onset and heterogeneity of the clinical and

electrophysiological features. Molecular analysis demonstrated a novel

heterozygous T/A transversion in the exon 3 of MPZ gene that predicts an

Asp109Glu amino acid substitution in the extracellular domain of the P0.

Asp109 is found at the protein surface, on beta strand E, in the

interior of the P0 tetramer.

CONCLUSIONS: The identification of Asp109Glu mutation confirms the

pivotal role of P0 in axonal neuropathies and stresses the phenotypic

heterogeneity associated with MPZ mutations. This study suggests the

value of screening for MPZ mutations in CMT family members with minor

clinical and electrophysiological signs of peripheral neuropathy.