2005 Fiscal Year Final Research Report Summary
Molecular Basis of Hereditary Neuropathy
| Project/Area Number |
16591008
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Yamagata University |
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Principal Investigator |
HAYASAKA Kiyoshi Yamagata University, School of Medicine, Professor, 医学部, 教授 (20142961)
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| Co-Investigator(Kenkyū-buntansha) |
SHIIHARA Takashi Yamagata University, University Hospital, Assistant Professor, 医学部, 助手 (90372333)
白幡 恵美 山形大学, 医学部, 医員 (60400553)
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| Project Period (FY) |
2004 – 2005
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| Keywords | hereditary neuropathy / Charcot-Marie-Tooth disease / sodium channel / PRX / MFN2 / HSP27 / distal hereditary motor neuropathy |
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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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Research Products
(9 results)
