Analysis Of PMP22 Duplication Mutation And Clinical Research Correlated With CMT1A

BACKGROUND AND OBJECTIVESCharcot- Marie -Tooth disease(CMT)is the most frequent single-gene inherited peripheral neuropathy,with clinical variability and genetic heterogeneity.A 1.5-Mb microduplication containing the gene for Peripheral Myelin Protein 22(PMP22) on chromosome 17p11.2-12 is responsible for CMT1A,which constitutes about 50-70%of Charcot- Marie -Tooth disease(CMT).Besides CMT1A,mutation of PMP22 may found in Dejerine-Sottas disease,Roussy-Levy syndrome,congenital hypomyelinating neuropathy.Deletion of PMP22 causes hereditary neuropathy with liability to pressure palsies(HNPP).So far,the method designed to detect PMP22 mutation is the most important for diagnosis of inherited peripheral demyelinating neuropathy.We combined allele-specific PCR-restriction enzyme digestion and Short Tandem Repeat(STR) analysis to detect PMP22 duplication.We also study the clinical variability and genetic heterogeneity of the CMT patients.MATERIALS AND METHODS1,Performed clinical examination in 45 patients diagnosed probalble CMT,and collected their information and blood.2,Combined allele-specific PCR-restriction enzyme digestion and Short Tandem Repeat(STR) analysis to detect PMP22 duplication.RESULTS1,The specific junctional fragments were amplified in 21 patients with allele-specific PCR,and checked with restriction enzyme digestion.2,Fourteen patients were positive in analysis of Short Tandem Repeat(STR).3,Combined use of the two methods,14 patients were detected of PMP22 duplication. Other 7 patients were positive for method 1 but could not identified by method 2.4,Eleven cases have PMP22 duplication in 15 typical CMT1 cases;6 CMT2 and 1 CMTX cases have not PMP22 duplication;10 cases have PMP22 duplication in 23 cases which were difficult to classify. CONCLUSIONS1,About 50%samples of our study have PMP22 duplication,which is similar to the reports of other groups in this field.2,Combined use of the allele-specific PCR-restriction enzyme digestion and short Tandem Repeat(STR) analysis provide a convenient,rapid and reliable method for PMP22 duplication detection.3,Charcot- Marie -Tooth disease(CMT) is a group of inherited neuropathy with high clinical variability and genetic heterogeneity.