摘要肝豆状核变性,即WilSon病,是一种由铜离子转运ATP酶β肽(ATPase Cu2+ transporting beta polypeptide,ATP7B)基因突变导致的常染色体隐性遗传的铜代谢障碍性疾病.现归纳总结不同突变的致病机制,包括诱导突变蛋白错误定位、改变蛋白间或结构域间相互作用、调控ATP7B蛋白催化活性、改变ATP7B基因剪接方式等多个方面.临床上,系统总结了常见突变与临床表型间的关联,如p.R778L,被认为与更加严重的临床症状相关;同时,环境、饮食、生活习惯等因素的差异亦可能对患者是否发病或发病时间产生较大影响.在分子层面上对ATP7B基因突变致病机制及所致临床表征的研究进行综述,将有助于加深对肝豆状核变性发病机制的认识,并提示可针对不同的机制采用个性化的诊疗手段,以指导临床实践.

abstractsHepatolenticular 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 ofATP7B 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 ofATP7B 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.