Rapid quantitative PCR diagnostic strategy for Charcot-Marie-Tooth 1A and hereditary neuropathy with liability to pressure palsies.

Charcot-Marie-Tooth (CMT) disorders are an extremely heterogeneous group of diseases of the peripheral nervous system in humans, with a prevalence of around 1 in 2,500. To date, mutations in 30 genes have been reported in various CMT forms. In numerous CMT types, only the locus is known, but some CMT forms were shown not to be linked with any known locus. Genetic studies in CMT disorders cover a wide spectrum of problems ranging from identification of novel mutations through studies of the pathogenic nature of mutations to genotype–phenotype correlations. CMT type 1 (CMT1) is a genetically heterogeneous group of chronic demyelinating polyneuropathies with loci mapping to chromosome 17 (CMT1A), chromosome 1 (CMT1B), chromosome 16 (CMT1C), and chromosome 10 (CMT1D). CMT1A is most often associated with a tandem 1.5-megabase (Mb) duplication in chromosome 17p11.2-p12. Rarely, it may result from a point mutation in the peripheral myelin protein-22 (PMP22) gene. CMT1B is associated with point mutations in the myelin protein zero (Po or MPZ) gene. Mutations in the SIMPLE gene cause CMT1C, and CMT1D is the result of mutations in the early response 2 (ERG2 or Krox-20) gene. An X-linked form of CMT1 (CMT1X) maps to Xq13 and is associated with mutations in the connexin32 (Cx32) gene. CMT neuropathy type 2 (CMT2) is an axonal neuropathy that maps to chromosome 1p35-p36 (CMT2A), chromosome 3q13-q22 (CMT2B), chromosome 7p14 (CMT2D), chromosome 8p21 (CMT2E), chromosome 1q22q23 (CMT2F), or chromosome 3q13 (CMT2G). Rapid Quantitative PCR Diagnostic Strategy for Charcot-Marie-Tooth 1A and Hereditary Neuropathy with Liability to Pressure Palsies