| Research Abstract |
Charcot-Marie-Tooth disease (CMT) is a most common hereditary neuropathy. CMT type 1 (CMT1), the major form of the disease, is a genetically heterogeneous disease and many responsible genes have been identified. However, disease-causing mutations have not been identified in many Japanese patients. We tried to establish the reliable and easy diagnostic method to make clear the molecular basis of Japanese patients. We also studied physiological properties of Nav 1.6 channel, which plays a significant role for signal transduction in the peripheral nervous system.
We studied 143 patients with CMT1 and initially identified the CMT1A duplication in 40 patients. As for the patients without the CMT1A duplication, we screened the mutations of PMP22, Po, Cx32, EGR2, LITAF, GDAP1, MTMR2 and PRX using denaturing gradient gel electrophoresis (DGGE) and denaturing high performance liquid chromatography (DHPLC). We identified 7 patients with PMP22 mutations, 16 patients with Po mutations, 13 patients with Cx32 mutations, 1 patient with EGR2 mutation, 1 patient with MTMR2 and 3 patients with PRX mutations. Compared with the data from foreign countries, the patients due to CMT1A duplication were few and many patients (44%) were not identified their etiologies. Further study is needed to clarify the molecular basis of Japanese patients.
We previously isolated cDNA of Nav 1.6 channel and examined biophysical properties of Nav 1.6 in heterologous expression cell systems using patch clamp method. We observed large persistent current of Nav 1.6 Channel in tsA201 cells however, the persistent current was significantly reduced by the co-expression with ankyrin G. It suggested that modulation by ankyrin G may underlie site-dependant electrophysiological Characteristics of Nav 106 channels.
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