肝豆状核变性的遗传学研究进展  

Genetic Research Advances of Wilson Disease

作　　者：杨华荣[1] 宋治[1] 邓昊[1] 

机构地区：[1]中南大学湘雅三医院神经内科医学实验中心,长沙410013

出　　处：《国际遗传学杂志》2009年第6期444-448,共5页International Journal of Genetics

基　　金：基金项目：国家自然科学基金项目（30871351,30971534）,湖南省杰出青年基金（09JJ1005）;周家教育部新世纪优秀人才基金（NCET-080563）

摘　　要：肝豆状核变性（Wilson’sdisease，WD）是一种铜转运障碍的常染色体隐性遗传病，以胆汁铜排泄及血浆铜蓝蛋白合成障碍而导致肝和肝外组织铜的过度蓄积为特征，进而出现肝硬化、豆状核变性和角膜的K—F环等一系列异常临床表现。WD是由ATP7B基因突变引起的，基因变异超过515种（至少379种可能为致病突变），广泛分布不同人种和地域，包括错义突变、无义突变、缺失突变、插入突变、置换突变和剪接突变等。其中最常见的突变类型欧洲患者为14号外显子His1069Gln错义突变，亚洲患者为位于8号外显子的Arg778Leu错义突变。基因突变分析有利于准确诊断及早期治疗，遗传缺陷的动物模型有助于开展实验性治疗和研究疾病的病理遗传机制。本文就肝豆状核变性的遗传学进展作一综述。Wilson disease （WD）, an autosomal recessive disorder of copper transport, is characterized by excessive accumulation of intracellular copper in liver and extrahepatic tissues because of impaired biliary copper excretion and disturbed incorporation of copper into ceruloplasmin, subsequently presence clinical mani- festations such as liver cirrhosis, lenticular degeneration and Kayser-Fleischer corneal rings. Mutations in the A TP7B gene are responsible for WD and more than 515 variants （379 probable disease-causing） have now been reported in patients with WD. The disease is distributed widely in different ethnic and geographical populations. The mutations include missense, nonsense, deletions, insertions, substitutions and splice mutations, etc. Missense mutation His1069Gln in exon 14 is the most common type of mutation in European patients, whereas, missense mutation Arg778Leu in exon 8 is the most frequently observed mutation type in Aisan patients. Gene mutation analysis contributes to accurate and definitive diagnosis, and early treatment. Animal models of genetic defects will help to carry out experimental treatment and elucidate pathological genetic mechanisms of this disease. The known genetic research advances in Wilson＇ s disease are reviewed in this article.

关 键 词：肝豆状核变性 遗传 基凶突变 ATP7B 动物模型 

分 类 号：R742.4[医药卫生—神经病学与精神病学] R394[医药卫生—临床医学]