MPZ Gene Mutation Detection And The Phenotype Analysis In Chinese CMT Patients

Background and purpose:Charcot-Marie-Tooth disease (CMT) ranks among the most common inherited neurological disorders. Clinically it is characterized by progressive muscle weakness and atrophy of extremities, distal sensory loss, pes cavus and absent deep tendon reflexes. On the basis of electrophysiological and pathological features, CMT is subdivided into three main groups:the demyelinating form (CMT1), the axonal form (CMT2) and the intermediate form. CMT is a monogenic disease, CMT IB phenotype caused by MPZ mutation accounts for5%of CMT1, and CMT2I/J phenotype associated with MPZ mutation accounts for5%of CMT2. Furthermore, more and more cases about intermediate CMT caused by MPZ mutation have been reported and the proportion has never been reported, however, it is the second common gene of intermediate CMT in addition to Cx32. We detected MPZ gene mutation in a cohort of70CMT patients collected in the past10years and generalized the clinical features of the patients with verified MPZ gene mutation.Methods:we detected MPZ mutation by means of polymerase chain reaction (PCR) and DNA direct sequencing.Results:1. We found4different missense mutations in4families and one sporadic patient:c.194C>T, c.242A>T, c.371C>T, c.419C>G. Mutations c.242A>T and c.419C>G have never been reported previously, c.371C>T is the hot spot mutation.2. The novel mutation c.242A>T exhibited late onset and rapidly progressive CMT2phenotype, while the novel mutation c.419C>G exhibited relatively late onset and slowly progressive CMT1phenotype.3. The clinical features of these CMT patients with MPZ mutation reported before have similar manifestations to those cases reported before. However, the2families with the MPZhot spot mutation (c.371C>T) had no Adie’s pupils and hearing loss.Conclusion:1. The MPZ mutation rate in our study was approximately4.35%of the total,3.08%of CMT1,6%of CMT2.2. The MPZ mutation should be firstly detected in these CMT2patients whose characteristics of late onset, rapid progressiveness and severe paresthesia.3. The MPZ mutation should be firstly detected in these CMT1patients with features of relative late onset and slow progressiveness.