The etiology of inborn error of copper metabolism, new method of treatment, and function of P-type copper transporting ATPase

1.门克斯病基因（ATP-7A）蛋白和威尔逊病基因（ATP-7B）蛋白的细胞内铜转运：细胞内铜浓度的增加导致ATP-7A和7B蛋白快速移动到细胞质囊室。这种铜特异性的ATP-7A和7B蛋白的细胞再分配是一个独立于新蛋白（铜的小泡运输）发生的可逆过程。日本威尔森氏病患者的分子分析威尔森氏病的突变谱可能显示一种人群依赖的模式。Wilson病的基因型与临床特征的相关性Wilson病的表型差异取决于Wilson病蛋白的功能水平。蛋白质的功能受基因突变类型（基因型）的调节。四硫钼酸盐（TTM）的掺杂作用TTM可与铜螯合，螯合产物不随尿液排出，而随胆汁排出。通过ATP7B基因分析Wilson病的家族性我们对Wilson病患者的家族成员进行ATP7B基因的家族性分析，发现了一名症状前患者和携带者。基因分析有助于发现肝豆状核变性的患者和携带者。建立症状前型肝豆状核变性诊断标准我们试图建立症状前型肝豆状核变性的诊断标准。

1.The intracellular copper transport of Menkes disease gene (ATP-7A) protein and Wilson disease gene (ATP-7B) proteinAn 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 diseaseThe mutation spectrum of Wilson disease may indicate a population-dependent pattern.3.The corelationship between genotype and clinical features in Wilson diseaseThe 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 analysisWe 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 diseaseWe attempted to establish doagnosis criteria for presymptomatic patients with Wilson disease.