Clinical And Genetic Spectrum In An Eastern Chinese Series Of Patients With Charcot-Marie-Tooth Disease

Objectives:To represent the clinical feature, electrophysiological data and genetic distribution of a series of patients with Charcot-Marie-Tooth disease in the Eastern China. And to determine the relationship between the clinical indicator and comparison between genotype and phenotype.Methods:All study subjects were patients meeting the clinical diagnosis of CMT who visited the Huashan Hospital, Shanghai, and the First Affiliated Hospital of Fujian Medical University from 2007-2013.148 families were included. Probands were ascertained by standard clinical and electrophysiological evaluation. Genomic DNA was extracted from peripheral venous blood, with standard method. MLPA was performed to detect the duplications/deletions of the PMP22 gene. The coding regions and splice sites of the GJB1, MPZ, MFN2 and GDAP-1 genes were also screened. Clinical data were analyzed and compared among the genetic subtypes.Results:1 Clinical and electrophysiological feature.Male to female ratio was 1.4:1. The median age visiting the clinic was 24 years old. CMT1 is more common than CMT2 and HNPP (54.1%,28.8% and 17.1%) in this series. Patients with certain family history accounting for nearly half (45.0%) of all the cases, AD was the most common inheritance pattern. Approximately 60% of cases symptoms onset in the first two decades of life with slow progression. Most patients in our series presented with some or all of the classic phenotype of CMT, such as distal atrophy and weakness, sensory loss, hyporeflexia, and foot deformity, symptoms start from the lower extremitas. Unusual signs also occur. Such as the upper limbs involvement as initiative symptom, cranial nerves involvement and pyramidal sign et al. The disease-related disabilities (CMTNS) were correlated with the course of disease in CMT1, but not with the age at onset. In the majority of cases, moderate elevation (178-400U/L) of CPK was observed.2 Genetic distribution.PMP22 duplication (13.5%) predominate in this group of patients, follow by PMP22 deletion (11.5%), point mutations in GJB1 (8.8%), MPZ (2.0%) and MFN2 (0.7%).No mutation was detected in GDAP1 gene. Mutations mostly occur in the exon 3 of MPZ gene in Chinese CMT patients. Four novel mutations in GJB1 gene were detected.3 Comparison between genotype and phenotype.Most patients with CMT1A have positive family history and presented with the well-known symptoms. Median MNCVs were usually slowed below 30 m/s, half of cases were even below 20m/s. Patients with Weakness of the limbs after sleeping was the most common chief of HNPP, recurrence of the symptoms or weakness in childhood occur in some cases, but some patients may present with the normal phenotype before the onset. In patients with HNPP electrophysiological data achieved high conformity with the result of gene testing (89.5%). In CMTX patients, men were affected more severely than women, the MNCVs were normal or slightly reduce (>30m/s) in all the cases. Patients with MPZ mutation can be divided into two distinct phenotypes:a severe, early-onset form or a late-onset mild axonal neuropathy, even with the same mutation loci.Conclusions:Distribution of the electrophysiological subtypes of CMT is similar between China and the European countries. Disease-related disabilities was correlated with the course of disease and CMAPs in CMT1. The frequency of PMP22 duplication in China and other Asia country seems lower than the European, South/North American, and Oceania. We suggest the genetic test strategies should primarily base on the electromyography data.