| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
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 have not been identified in many patients. In addition, the genotype-phenotype relationship is unknown. We established the reliable and easy diagnostic method using denaturing high performance liquid chromatography (DHPLC) and studied many Japanese patients.
We studied 67 patients with demyelinating CMT who have no mutation in PMP22, Po, Cx32 and FGR2. We screened LITAF, GDAP1, MTMR2, PRX and DRP2 using DHPLC. We identified 4 patients with PRX mutations ; 3 homozygotes for R1070X and one compound heterozygote for R1070X and L132FsX153. The patients with PRX mutations showed early onset but no or slowly progressive symptoms.
We studied MFN2, HSP22, HSP27, MFN1 and DRP1 in 76 Japanese patients with axonal or unclassified CMT or distal hereditary motor neuropathy (dHMN). We detected 7 mutations of MFN2 in 7 unrelated patients; R94Q, T236M, F223L, V244M, F284Y, K357N and E424G. We also found the P182S mutation of HSP27 in one patient with dHMN.
MFN1, MFN2 and DRP1 play a significant role in the fusion of mitochondria, however, MFN2 is an only disease-causing gene of CMT. We cannot identify a disease-causing gene in many patients with CMT. Further study is needed to clarify the molecular basis of CMT.
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