| Project/Area Number |
13670638
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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 |
Neurology
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| Research Institution | SHINSHU UNIVERSITY |
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Principal Investigator |
TAKEI Yo-ichi SHINSHU UNIVERSITY, assistant, 医学部, 助手 (90273086)
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| Co-Investigator(Kenkyū-buntansha) |
IKEDA Shu-ichi SHINSHU UNIVERSITY, professor, 医学部, 教授 (60135134)
TOKUDA Takahiko SHINSHU UNIVERSITY, lecturer, 医学部, 助教授 (80242692)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | familial amyloid polyneuropathy / transthyretin / domino liver transplantation / mass spectrometry / transthyretin monomer / 肝移植 / ドミノ移植 / モノマー |
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| Research Abstract |
We have diagnosed 20 familial amyloid polyneuropathy (FAP) patients and 5 FAP carriers since 2001. Most of these patients were diagnosed as having Val30Met transthyretin (TTR) mutation. We found a rare case with carpal tunnel syndrome and severe cardiac amyloidosis, whose ATTR Tyr69Ile was found to be caused by double-nucleotide substitution at codon 69.
Twenty liver transplantations have been performed since 1993 in patients with FAP, including 5 domino liver transplantations. After the operation the serum concentration of mutant type TTR is increased promptly in domino recipients. Serial examinations of clinical findings and abdominal fat aspiration biopsy were performed for them after the operation. However, no sign of polyneuropathy, autonomic neuropathy and amyloid deposition was detected respectively. In FAP patients, mass spectrometry showed that the variant monomer was markedly decreased compared with the wild-type TTR monomer. In domino recipients who were transplanted FAP liver, variant monomer was not decreased. These findings suggest that the free variant TTR monomer is unstable in serum, and that it aggregates in deposits in various organs in FAP patients. However, in domino recipient amyloid deposition or amyloid fibril formation has not yet started within two or three years after operation. It is suggested that free variant TTR monomer is useful to know the beginning of amyloid deposition.
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