| Project/Area Number |
10670764
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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 | Toho Unversity School of Medicine |
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Principal Investigator |
SHIMIZU Norikazu Toho Univ., 2nd Dept. of Pediatrics, Assistant professor, 医学部, 講師 (60256740)
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| Co-Investigator(Kenkyū-buntansha) |
HEMMI Hiromichi Toho Univ., Dept. of Molecular Biology, Associate professor, 医学部, 助教授 (90165514)
YAMAGUCHI Yukitoshi Toho Univ., 2nd Dept. of Pediatrics, Assistant professor, 医学部, 講師 (30277339)
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| Project Period (FY) |
1998 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | inborn error of copper metabolism / Wilson disease / Menkes disease / ATP7A / ATP7B / molecular analysis / copper induced ATPase activity / genotype-phenotype correlation / ATP7B / 遣伝子解析 / 遺伝子変異と病型 / 血清セルロプラスミン値 / ATPase活性 / 銅輸送P-type ATPase / 銅輸送P-type ATRase |
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| Research Abstract |
1. Molecular analysis for Wilson disease patients and Menkes disease patients in Japan
We analyzed ATP7B gene for 40 Japanese Wilson disease patients and ATP7A gene for 2 Japanese classical Menkes disease patients. R778L, A874V and 2871delC mutations were common mutations in Japanese Wilson disease patients.These 3 mutations could be found more than 50% of alleles. Also, we found novel mutation of Menkes disease patient, 2491insA. Mother of this patients had no mutation. Thus this mutation was de novo mutation.
2. Genotype-phenotype correlation of Wilson disease
All of the patients who had R778L mutation homozygously were neurologic type of Wilson disease. Also all of patients who had 2871delC mutation homozygouly revealed severe liver dysfunction and/or progressive liver failure. We speculate that R778L mutation is specific for neurologic phenotype and 2871delC mutation causes svere hepatic damage.
3. Copper specific P-type ATPase activity
Copper-induced ATPase activities were measured relative to the lymphoblast cell lines derived from one case of classical Menkes disease patient and his mother, five Japanese patients with Wilson disease, and two normal subjects were investigated. Loss of copper-induced ATPase activities in lymphoblast were 29.1 ± 4.2% (Menkes disease patient), 48.2 ± 1.9% (his mother) and 42.7-60.8% (Wilson disease patients). In this study, copper-induced ATPase activities of Menkes disease patient, carrier of this disease and Wilson disease patients were definitely lower than that of normal subjects. This method will be useful as a functional analysis for copper metabolic disorders.
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