The 17p11.2 duplication and Connexin 32 (Cx32) mutations are the most frequent gene mutations responsible for Charcot-Marie-Tooth diseases. We classified 282 Charcot-Marie-Tooth families according to the median motor nerve conduction velocity of the index patient and the mode of inheritance, and screened them for 17p11.2 duplication and Cx32 mutations. Forty-seven percent of the Charcot-Marie-Tooth families had median motor nerve conduction velocity under 30 m/s (group 1), 15% between 30 and 40 m/s (group 2), and 28% over 40 m/s (group 3). Spinal Charcot-Marie-Tooth (group 4) was observed in 7% of the families. Modes of inheritance were not similarly represented among the different groups. The 17p11.2 duplication was detected in index patients of group 1 only, and accounted for 83% of the familial cases and 36% of the isolated cases. In contrast, 21 Cx32 mutations were detected to variable degrees in groups 1-3, but were most numerous by far in dominant families of group 2 (44%). This systematic approach was taken to estimate the frequency of 17p11.2 duplication and Cx32 mutations in the different Charcot-Marie-Tooth subgroups, in order to propose a practical strategy for molecular analysis.