The frequency of 17p11.2 duplication and Connexin 32 mutations in 282 Charcot-Marie-Tooth families in relation to the mode of inheritance and motor nerve conduction velocity

Abstract

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.