Grant-in-Aid for Scientific Research (B).
|Research Institution||Toho University School of Medicine|
AOKI Tugutoshi Toho Univ., 2nd Dept.of Pediatrics, Professor, 医学部, 教授 (50057585)
内山 利満 東邦大学, 医学部, 教授 (50057709)
嶋武 博之 東邦大学, 医学部, 教授 (40010110)
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)
SHIMIZU Norikazu Toho Univ., 2nd Dept.of Pediatrics, Assistant professor, 医学部, 講師 (60256740)
UCHIYAMA Tishimitu Toho Univ., Dept.of Pharmacology, Professor
SHIMATAKE Hiroyuki Toho Univ., Dept.of Molecular Biology, Professor
|Project Fiscal Year
1997 – 1999
Completed(Fiscal Year 1999)
|Budget Amount *help
¥8,500,000 (Direct Cost : ¥8,500,000)
Fiscal Year 1999 : ¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1998 : ¥3,000,000 (Direct Cost : ¥3,000,000)
Fiscal Year 1997 : ¥3,400,000 (Direct Cost : ¥3,400,000)
|Keywords||inborn error of copper metabolism / Wilson disease / ATP7A / ATP7B / gene analysis / molecular diagnosis / tetrathiomolybdate (TTM) / presymptomatic diagnosis / 遺伝性銅代謝異常症 / Wilson病 / 遺伝子解析 / 遺伝子診断 / テトラチオモリブテン(TTM) / 発症前診断 / 銅特異的ATPase活性 / テトラチオモリブデン(TTM) / 遺伝性銅代謝異常 / Menkes病 / 銅輸送P-type ATPase / Tetrathiomolybdate (TTM)|
1.The intracellular copper transport of Menkes disease gene (ATP-7A) protein and Wilson disease gene (ATP-7B) protein
An increase in the intracellular copper concentration results in the rapid movement of ATP-7A and 7B proteins to a cytoplasmic vesicular compartment. This copper-specific cellular redistribution of ATP-7A and 7B protein is a reversible process that occurs independent of new protein (small vesicles of copper transport).
2.Molecular analysis for Japanese patients with Wilson disease
The mutation spectrum of Wilson disease may indicate a population-dependent pattern.
3.The corelationship between genotype and clinical features in Wilson disease
The difference of phenotypes of Wilson disease depend on functional levels of Wilson disease protein. And protein function is regulated by types of gene mutations (genotype).
4.Doppering effect of tetrathiomolybdate (TTM)
TTM may chelate with copper and chelated product will be excreted in the bile, not in the urine.
5.Familial analysis of Wilson disease by ATP7B gene analysis
We performed familial analysis of ATP7B gene of family members of Wilson disease patient, and found a presymptomatic patient and carrier. Gene analysis is useful to detect patients and carriers with Wilson disease.
6.Establish of diagnostic criteria for presymptomatic type of Wilson disease
We attempted to establish doagnosis criteria for presymptomatic patients with Wilson disease.