Mutation testing in Charcot-Marie-Tooth neuropathy

In order to determine the optimal approach for mutation testing in the form of Charcot-Marie-Tooth (CMT) neuropathy, consecutive patients with a CMT phenotype, available family history information on at least first-degree relatives, and median motor conduction velocities of less than 50 m/sec were tested for the CMT1A duplication and for connexin32, peripheral myelin protein 22 (PMP22) and myelin protein zero (P0) point mutations. A cutoff value for median motor conduction velocity of less than 50 m/sec was adopted to include all CMTX families. All of the connexin32 mutations, except for one sporadic case, were found by first selecting families with no male-to-male inheritance of CMT and neurophysiological indicators of CMTX. All PMP22 and P0 mutations were found by selecting Dejerine-Sottas cases or dominantly inherited CMT1 with a very severe phenotype. It is concluded that "blind" testing of CMT1 families for connexin32, P0, and PMP22 mutations is of limited value.