CMT 1B: Gene dosage sensitivity of a novel mutation in the intracellular domain

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Neuromuscul Disord. 2006 Feb 17

Gene dosage sensitivity of a novel mutation in the intracellular

domain of P0 associated with Charcot-Marie-Tooth disease type 1B.

Fabrizi GM, Pellegrini M, Angiari C, Cavallaro T, Morini A, Taioli F,

Cabrini I, Orrico D, Rizzuto N.

Section of Clinical Neurology, Department of Neurological and Visual

Sciences, University of Verona, Policlinico G.B. Rossi, P.le L.A.

Scuro 10, 37134 Verona, Italy.

Autosomal dominant Charcot-Marie-Tooth disease type 1B (CMT1B) is

caused by heterozygous mutations in the extracellular domain of P0.

Here, we investigated clinically, electrophysiologically and

pathologically a pedigree with a novel mutation in the intracellular

domain of P0 (P0ic). The mutational analysis included denaturing high

performance liquid chromatography (DHPLC) and nucleotide sequencing.

Two patients from subsequent generations were homozygous for an

Asp195Tyr mutation in the intracellular domain of P0 (P0ic), whereas

two healthy individuals with minimal electrophysiological changes

were heterozygous for the same mutation. The authors conclude that

mutations of P0ic may undergo a gene dosage effect manifesting

semidominant inheritance.