1994 Fiscal Year Final Research Report Summary
abnormal transthyretin in FAP
| Project/Area Number |
05670564
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | Miyazaki Medical College |
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Principal Investigator |
NAKAZATO Masamitsu Miyazaki Medical College, Faculty of Medicine, Assistant Prof, 医学部, 助手 (10180267)
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| Project Period (FY) |
1993 – 1994
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| Keywords | FAP / transthyretin / DNA diagnosis / amyloidosis / DNA診断 / ラジオイムノアッセイ |
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| Research Abstract |
Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant inherited disorder characterized by progressive motor, sensory and autonomic polyneuropathy and by lethal cardiac and renal amyloidosis. Age of onset, progression of illness, genetic penetrance and main organ involvement considerably vary in subtypes of FAP.We have shown that the disease results from systemic deposition of amyloid fibril protein which consists of a variant transthyretin (TTR) with one amino acid substitution. We have found seven variant TTRs by amino acid sequence analysis in cooperation with many researchers in Japan and other countries. Their amino acid substitutions are Val^<30>*Met, Val^<30>*Leu, Phe^<33>*Ile, Thr^<60>*Ala, Glu^<61>*Lys, Ser^<77>*Tyr, and Ala^<97>*Gly. Point mutations in the TTR gene responsible for these substitutions were determined by direct DNA sequening. DNA diagnostic methods also were established by restriction fragment length polymorphism of amplified TTR exons or PCR-induced mutation restriction analysis. BIOCES analysis of the variant TTR molecules showed slight to drastic changes in their tertiary structure compared to the normal molecule, which may be related to mild to severe clinical manifestations in subtypes of FAP or to incomplete penetrance of clinical expression in some types of FAP.
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[Publications] Holmgren, G., Lundgren, E., Kangawa, K., Kurihara, T., Matsukura, S., Matsuo, H., Nakazato, M., and Steen, L.: "Diagnostic radioimmunoassay and DNA-analysis in Swedish and Japanese patients with familial amyloidotic polyneuropathy. Homozygosity for the TTR met^<30> gene." Acta.Neurol.Scand.87. 124-127 (1993)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Shiomi, K., Nakazato, M., Matsukura, S., Ounishi, A., Hatanaka, H., Tsuji, S., Murai, Y., Kojima, M., Kangawa, K., and Matsuo, H.: "A basic transthyretin variant (Glu^<61>*Lys) causes familial amyloidotic polyneuropathy : protein and DNA sequencing and PCR-induced mutation restriction analysis." Biochem.Biophys.Res.Commun.194. 1090-1096 (1993)
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「研究成果報告書概要(欧文)」より
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[Publications] Yasuda, T., Sobue, G., Doyu, M., Nakazato, M., Shiomi, K., Yanagi, T.and Mitsuma, T.: "A novel variant transthyretin (Ala^<97> to Gly) in a Japanese kindred with familial amyloidotic polyneuropathy." J.Neurol.Sci.121. 97-102 (1994)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamamoto, K., Hsu, S., Yoshida, K., Ikeda, S., Nakazato, M., Shiomi, K., ChengS., Furihata, K., Ueno, I., and Yanagisawa, N.: "Familial amyloid polyneuropathy in Taiwan : Identification of transthyretin variant (Leu*Pro^<55>) by DNA and amino acid sequences." Muscle Nerve. 17. 637-641 (1994)
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「研究成果報告書概要(欧文)」より
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[Publications] Ando, Y., Tashima, K.Tanaka, Y., Nakazato, M., Ericzon, B.-G., Duraj, F.F., Sakashita, N., Kimura, E., Ando, E., Yonehara, T., Yamashita, T., Nakamura, M., Uchino, M., and Ando, M.: "Treatment of a Japanese patient with familial amyloidotic polyneuropathy with orthotopic liver transplantation. transplantation." Int.Med.33. 730-732 (1994)
Description
「研究成果報告書概要(欧文)」より
