肝豆状核变性发病机制

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       肝豆状核变性是一种常染色体隐性遗传疾病,ATP7B是目前已知的唯一相关致病基因。ATP7B基因主要在肝细胞中表达,经内质网、高尔基体修饰加工后定位至高尔基体内膜,参与铜蓝蛋白的合成和铜的胆道排泄。当机体铜过量时,高尔基体以囊泡的形式向细胞膜转移,与细胞膜融合后将铜排到胆道。


      当ATP7B发生突变时,5'UTR区的突变会导致ATP7B的转录受到影响,无义、移码和剪切位点的突变常导致ATP7B翻译一个截短的ATP7B多肽链,而错义突变常导致蛋白折叠加工及细胞定位受阻,突变蛋白进入溶酶体降解,铜蓝蛋白合成障碍,胆道排铜出现障碍。

参考文献

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3.  Harada M,, Sakisaka S, Terada K, Kimura R, Kawaguchi T, Koga H, et al. A mutation of the Wilson disease protein, ATP7B, is degraded in the proteasomes and forms protein aggregates. Gastroenterology. 2001;120:967–74.

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