肝豆状核变性的临床特征及其分子诊断  

Clinical characteristics and molecular diagnosis of Wilson′s disease

作　　者：刘芸野[1] 谷雷雷[1] 黄道[1] 林之莓[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院感染科,上海200025

出　　处：《诊断学理论与实践》2014年第3期267-270,共4页Journal of Diagnostics Concepts & Practice

摘　　要：目的:观察肝豆状核变性患者的多样性临床表现,探讨建立分子诊断的方法。方法:采集62例肝豆状核变性患者的临床资料,包括临床表现、实验室检查和其他特征等,进行统计分析。应用序列分析方法检测ATP7B基因突变,并对p.Arg778Leu基因突变的基因型与表型的相关性进行分析。结果:27例(43.5%)患者诊断时年龄<8岁,且均缺乏典型的临床表现,仅有2例出现K-F环,而59.3%的患者仅表现为肝功能异常。与表现为肝脏疾病的患者相比,以神经系统为表现的患者诊断时年龄较大(P<0.000 1),诊断延期时间更长(P<0.000 1)。本组患者共检测到40个不同的基因突变,其中有14个为新发现的基因突变。肝豆状核变性的常见基因突变为p.Arg778Leu(31.9%)和p.Pro992Leu(11.2%)。另发现p.Arg778Leu纯合突变患者(n=7)在临床上更多表现为肝脏疾病,诊断时丙氨酸转氨酶水平更高,与p.Arg778Leu杂合突变(n=22;P=0.028)或其他基因突变患者(n=29;P=0.036 1)相比,差异有统计学意义。结论:在年轻患者特别是8岁以下的患儿中,基因检测是诊断肝豆状核变性非常有价值的方法,而突变类型可预测其疾病的临床表现。Objective： To investigate the clinical manifestations of Wilson＇s disease （WD） and establish the method of molecular diagnosis. Methods： Sixty-two WD patients were enrolled in this study. The clinical data including clinical manifestations, laboratory tests and other features were collected and analyzed statistically .The ATP7B gene mutation was analyzed by direct sequencing, and genotype-phenotype correlations with respect to p.Arg778Leu were studied. Results： Twenty-seven patients （43.5%）were children younger than 8 years at diagnosis. The children often lacked typical symptoms, and only 2 of the 27 patients presented with K-F ring, and 59.3% only had abnormal liver function. Neurologic manifestations were associated with older age at diagnosis （P〈0.000 1） and having longer diagnostic delay （P〈0.000 1）. Forty different mutations, including 14 novel mutations, were identified in this study. Mutations including p.Arg778Leu （31.9%） and p.Pro992Leu （11.2%） were commonly seen. The patients homozygous for p.Arg77gLeu mutation （n=7） demonstrated more hepatic manifestations and higher serum ALT levels at diagnosis than patients heterozygous for this mutation （n=22; P=0.028） or other mutations （n=29; P=0.036 1）. Conclusions： Genetic testing is a valuable method for diagnosis of WD in young children, especially in patients younger than 8 years old. The mutation type can predict clinical manifestations.

关 键 词：肝豆状核变性 基因突变 序列分析 诊断 

分 类 号：R589.9[医药卫生—内分泌]