Charcot-Marie-Tooth disease (CMT) (ORPHA166) is the most frequent hereditary neuropathy. CMT is a heterogeneous group of disorders which, despite some variability in their clinical features, share the same general phenotype, usually characterized by wasting and weakness of distal limb muscles, decreased to absent deep tendon reflexes, distal sensory loss, and frequent skeletal deformities. Despite the clinical and molecular description of this disease in the last 20 years, there is no effective drug or advanced therapy available. Here, the authors describe the identification of metabolic and oxidative stress biomarkers in the plasma of patients with duplication at PMP22 gene, the most frequent mutation causing CMT, and clinically characterized as CMT1A. The metabolic biomarkers were identified using 2D-DIGE analysis (Typhoon TRIO, GE) and DeCyder software (GE). Protein identification was made by mass spectrometry by MALDI-TOF-TOF (ABSciex) and liquid chromatography analysis (ABSciex). Identification of oxidative stress biomarkers consisted of carbonylated proteins analysis by reaction with DNPH and Dot-blot. Total antioxidant capacity and GSSG/GSH ratio were analyzed with Antioxidant Assay kit (Cayman) and Glutathione Fluorescent detection Kit (Arbor Assays), respectively. The authors found 8, 13 and 36 proteins with differential expression in mild, moderate and severely affected patients, respectively. Differences in oxidative stress parameters between the different groups analysed were also observed. These results suggest differences in the oxidative stress profile between the studied phenotypes in CMT1A patients.
