Charcot-Marie-Tooth (CMT) diseases include a group of clinically heterogeneous 
inherited neuropathies subdivided into demyelinating (CMT1), axonal (CMT2) and 
intermediate CMT forms. CMTs are associated with different genes, although 
mutations in some of these genes may cause both clinical pictures. To date, more 
than 50 CMT genes have been identified, but more than half of the cases are due 
to mutations in MFN2, MPZ, GJB1 and PMP22. The aim of this study was to estimate 
the frequency of disease mutations of these four genes in the axonal form of CMT 
in order to evaluate their effectiveness in the molecular diagnosis of CMT2 
patients. A cohort of 38 CMT2 Italian subjects was screened for mutations in the 
MFN2, MPZ and GJB1 genes by direct sequencing and for PMP22 rearrangements using 
the MLPA technique. Overall, we identified 15 mutations, 8 of which were novel: 
11 mutations (28.9 %) were in the MFN2 gene, 2 (5.3 %) in MPZ and 2 (5.3 %) in 
PMP22. No mutations were found in GJB1. Two patients showed rearrangements in 
the PMP22 gene, which is commonly associated with CMT1 or HNPP phenotypes thus 
usually not tested in CMT2 patients. By including this gene in the analysis, we 
reached a molecular diagnosis rate of 39.5 %, which is one of the highest 
reported in the literature. Our findings confirm the MFN2 gene as the most 
common cause of CMT2 and suggest that PMP22 rearrangements should be considered 
in the molecular diagnosis of CMT2 patients.