Function Disability And Genetics Research In Pediatric Charcot-marie-tooth Patients

BACKGROUNDS AND OBJECTIVESCharcot-Marie-Tooth disease（CMT）is the most common inherited peripheralneuropathy, the incidence is about1/2500. It can be slowly progressive and willgreatly influence life qualities of these patients. Now there’re Charcot-Marie-ToothNeuropathy Score in2005and the CMT Pediatric Scale in2012to evaluate thefunction disabilities of CMT patients in abroad. While in China, there’re still no validoutcome measures to investigate the function disabilities of CMT patients. CMT isslowly progressive; with some patients get the disease in the early stage of childhood.A valid outcome measure is very essential to improve the survival quality of thesepatients and also to the doctors to choose the treatment solutions.As the rapid development of molecular test, until now, more than43pathogenicgenes related to Charcot-Marie-Tooth have been reported. Genetic epidemiology ofCharcot-Marie-Tooth, the results showed PMP22, MPZ, MFN2, GJB1and GDAP1are the mainly pathogenic gene in CMT, So the screening of the five genes above inCMT patients is of great significance.The objectives of our study are as follows:1) Evaluating the function disabilitiesof pediatric CMT patients, to investigate its characteristics, factors that may influencethe function disabilities in children.2) Screening for mutation rates of PMP22geneduplication mutation and MFN2, GJB1, MPZ, GDAP1gene point mutation.3)Discussing the relationship between genotype, phenotype and electrophysiologicaltest.METHODS1. Collect the clinical data of pediatric CMT patients admitted to Beijing Children’ sHospital during1996-2013. 2. Use the FDS, MNDS and CMTNS to evaluate function disability of thesepatients.3. Use the MLPA or RCR-REPs to screen the PMP22gene duplication mutation, andPR combined DNA direct sequencing to screen point mutation of MFN2, GJB1,MPZ and GDAP1gene.4. Use the SPSS19.0and Excel2007software to analyze the data.RERULTS1. Feet deformity can become complicated as patients grow up. Function disabiltyin CMT children evaluated by FDS and CMTNS are in mild-moderate level.Patients with high FDS get higher CMTNS.2.6in15CMT1patients have PMP2gene duplication mutation.7in33CMT2patients have MFN2point mutation (c.1090Câ†'T(Arg364Trp) andc.280Câ†'T(Arg94Trp) have been reported, the other five are de novo mutations).4in13DI-CMT patients have GJB1gene mutation (all of the mutation site arede novo mutations).2in18CMT patients have MPZ genemutation(c.292C>T(Arg98Cys) has been reported before).1in7sporadicpatients have GDAP1mutation(c.767Aâ†'G(His256Arg) has been repaoted inChina).3. Function disability in PMP22gene duplication mutation children is much milderthan other four pathogenic genes. Children with MPZ point mutation get the mostsevere function disability. Function disability in MFN2gene and GJB1genemutation differs a lot.4. Nerve conduction velocity decreased consistency in CMT1A patients, while inCMT2A patients electrophysiological change is charicterised by reducedamplitude of CMAP and SNAP. Electrophysiological change of CMTX isbetween CMT1and CMT2. CONCLUSIONS1. The CMTNS has a good consistence in evaluating function disability with FDS.CMTNS is a valid method to evaluate function disability in children about10years old. Early diagnosis and treatment are important for CMT children.2. The mutation rate of PMP22gene duplication in patients who accepted gene testis12.2%, while the mutation rate of MFN2, GJB1, MPZ and GDAP1gene pointmutation are12.2%,8.2%,4.1%,2%seperately. Gene diagnosis rate in CMTpatients is38.8%.3. CMT is a kind of highly heterogeneous disease in genotype-phenotype, but it hasa good consistence with genotype and electrophisilogical tests.