Abstract: Objective To identify the pathogenic mutation in a large Chinese family with Charcot-Marie-Tooth disease (CMT). Methods Medical history of the proband and a detailed family history were collected. Necessary physical examination and nerve conduction velocity/EMG testing were performed to establish the diagnosis of CMT and a primary classification. Genomic DNA was extracted from peripheral blood samples of 16 family members. Five genetic loci for six CMT1 subtypes were screened by linkage analysis using microsatellite markers. Quantitative PCR was used to detect the genomic duplication encompassing the peripheral myelin protein 22 gene (PMP22). Results The CMT phenotype was transmitted in this family in an autosomal dominant pattern. Slow nerve conduction velocity (10-30m/s) was observed in all of the four patients who participated in the electrophysiologic testing. By linkage analysis, all CMT1 subtypes were excluded except the CMT1A and CMT1E locus, both of them involving the PMP22 gene on chromosome 17p11.2 region. Heterogeneous duplication of the PMP22 gene was detected in patients, but not in unaffected family members. Conclusion The disease in the family was ascertained to be CMT1A, and was caused by the PMP22 duplication.

Key words: Charcot-Marie-Tooth disease, PMP22, duplication, quantitative PCR