Detection of Charcot-Marie-Tooth Type 1A (CMT1A) Disease Using Multiplex Real-Time Assay

Charcot-Marie-Tooth disease (CMT) or Hereditary motor and sensory neuropathy (HMSN) and Hereditary neuropathy with liability to pressure palsy (HNPP) are genetically heterogeneous disorders of the peripheral nerves. Approximately 70 percent of patients reported with genetic related CMT are CMT1A, which is resulted from the genetic defect of peripheral myelin protein 22 ( PMP22 ) gene located on chromosome 17p11.2-p12. The most common mutation is duplication of PMP22 . Deletion is also occasionally observed. In this study, a comparative quantitative multiplex real-time PCR method was developed in order to accurately diagnose CMT1A and HNPP instead of using Southern blot analysis. A total of  33 patients with CMT were enrolled to this study and 7 out of 33 patients (21.2%) were identified 17p duplication. On the contrary, no 17p deletion was observed. All positive patients for 17p duplication had clinical phenotypes and electrophysiological abnormalities compatible with CMT1A. Quantitative real-time PCR was easy to set up, no radioactive use, reliable, consistent, and less time consuming compared to Southern analysis.In addition, the method also produces results which can be easily interpreted. In conclusion, the comparative multiplex real-time PCR can be used as a good replacement method for diagnosis of CMT1A and HNPP due to its simplicity and high cost effectiveness.