Objective To investigate the clinical manifestations of two families with Charcot-Marie-Tooth (CMT) disease and the characteristics of PMP22 gene duplication mutation in the Henan, China.Methods The clinical data of 21 members of the two families were collected, and allele-specific polymerase chain reaction (PCR) combined with double restriction-enzyme digestion was used to detect 17p11.2-1 PMP22 gene duplication (i.e., 1760 bp segment). A total of 50 healthy volunteers were enrolled as the control group.Results In these two families, 14 members had PMP22 gene duplication (i.e., 1760 bp segment) detected by allele-specific PCR combined with double restriction-enzyme digestion. In the first family, three members (II5, II7, III11) had this disease, and the results of gene detection showed 6 carriers of PMP22 gene duplication mutation (II9, III6, III8, III10, IV1, IV2), although they had no clinical symptoms. In the second family, four members (II3, II9, II11, III7) had this disease and there was only one carrier (III5). The above duplication mutation was not detected in the other 7 members or 50 healthy controls.Conclusions PCR-double restriction-enzyme digestion for the detection of PMP22 gene duplication plays an important role in the early diagnosis of CMT.