Charcot-Marie-Tooth neuropathy type 1A with both duplication and non-duplication

We studied a family with nine of twenty members affected with Charcot-Marie-Tooth disease type 1A (CMT1A). The proband and her four affected sibs showed no duplication of the 17p11.2-p12 (CMT region). Two of the proband's affected daughters and three affected grandchildren showed duplication of the PMP-22 gene and of the marker VAW409R3 but not of the markers VAW412R3 and EW401. Pulsed field gel electrophoresis (PFGE) revealed a 220 kb SacII fragment in one CMT1A patient with duplication instead of a 500 kb SacII fragment as previously reported (1, 3, 4, 6-9). Our findings suggest a smaller size of the duplication in this CMT1A family. The disease segregates with the same haplotype in both duplicated and nonduplicated CMT1A patients. The clinical phenotype showed more severe weakness with earlier onset and motor nerve conduction velocities were characterized by more significant slowing in the patients with duplication than in the patients who did not show duplication.