Jia S Y, Zhou D H, Ou X J, Huang J
Experiment Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China; Beijing Institute of Clinical Medicine, Beijing 100050, China.
Liver Disease Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050.
Zhonghua Gan Zang Bing Za Zhi. 2020 Feb 20;28(2):188-192. doi: 10.3760/cma.j.issn.1007-3418.2020.02.019.
Hepatolenticular degeneration, also named Wilson disease, is an autosomal recessive genetic disease that characterized by copper metabolism disorder. WD mainly caused by the dysfunction of mutant ATP7B variants. This review summaries the mechanisms that different mutations affect the function of ATP7B, including inducing the mislocalization of mutant proteins, affecting the interactions between proteins or domains, regulating catalytic activity of ATP7B, and modifying the splicing of ATP7B gene. Further more, the genotype-phenotype correlation of a few mutations has been reviewed. Several mutations, such as p.R778L, are considered to be associated with more serious clinical symptoms, and the differences in environmental, diet, and lifestyle habits may also have effects on the susceptibility or the onset age of the patients. The research of the pathogenesis and clinical characterization of ATP7B gene mutations in the molecular level helps to deepen the understanding of WD, and suggests that personalized treatments should be used in future clinical practice.
肝豆状核变性，也称为威尔逊病，是一种常染色体隐性遗传病，其特征为铜代谢紊乱。威尔逊病主要由突变的ATP7B变体功能障碍引起。本综述总结了不同突变影响ATP7B功能的机制，包括诱导突变蛋白的错误定位、影响蛋白质或结构域之间的相互作用、调节ATP7B的催化活性以及改变ATP7B基因的剪接。此外，还综述了一些突变的基因型-表型相关性。几个突变，如p.R778L，被认为与更严重的临床症状相关，环境、饮食和生活方式习惯的差异也可能对患者的易感性或发病年龄产生影响。在分子水平上对ATP7B基因突变的发病机制和临床特征进行研究有助于加深对威尔逊病的理解，并表明未来临床实践中应采用个性化治疗。
