Charcot-Marie-Tooth disease and related peripheral neuropathies

Abstract

Molecular genetic analysis of the demyelinating neuropathies Charcot-Marie-Tooth disease and hereditary neuropathy with liability to pressure palsies has uncovered a novel mutational mechanism whereby a reciprocal recombination involving a misaligned flanking repeat sequence results in both the Charcot-Marie-Tooth disease type-1A duplication and hereditary neuropathy with liability to pressure palsies deletion. These studies have illuminated the role that gene dosage may play in causing a disease phenotype, which has important implications for therapeutic strategies, and which may underlie the basis of the extreme clinical variability. The identification of these rearrangement mutations (duplication and deletion) has resulted in the availability of molecular procedures for establishing or excluding a secure diagnosis, enabling presymptomatic and prenatal diagnosis, and providing prognostic information. © 2006 Humana Press Inc.