Research and treatment of hereditary neuropathy

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Charcot-Marie-Tooth disease (CMT) is a most common hereditary neuropathy and is a genetically heterogeneous disease. Many responsible genes have been identified, however, disease-causing mutations had not been identified in many Japanese patients. So we established denaturing high performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA) methods for screening of major disease-causing genes. We studied many Japanese patients with no CMT1A duplication and detected 15 cases with MPZ mutations, 18 cases with GJB1 mutations, 6 cases with PMP22, 1 case with EGR2 mutations and 4 cases with PRX mutations in demyelinating CMT using DHPLC method. As for axonal CMT, DHPLC screening detected 3 cases with MPZ mutations, 2 cases with GJB1 mutations and 10 cases with MFN2 mutations. In addition, DHPLC screening detected 2 cases with HSP27 mutations in distal hereditary motor neuropathy. MLPA screening did not detect a change in gene copy numbers except for CMT1A (PMP22) duplication. Nine cases were found to have CMT1A duplications and 3 of them had not been found by Southern blot hybridization or FISH methods. Our study confirmed that a change in gene copy numbers except for PMP22 is not a cause of CMT and MLPA is more sensitive to detect CMT1A duplication than Southern blot hybridization or FISH methods.