肝豆状核变性患者的临床表型和ATP7B基因变异分析

Analysis of clinical phenotype and ATP7B gene variation with wilson disease

目的:分析我国北方部分地区肝豆状核变性(wilson disease,WD)患者的临床特征及ATP7B基因变异情况。方法:以2018年11月至2022年4月期间在河南大学附属郑州颐和医院确诊的50例WD患者为研究对象,提取患者外周血基因组DNA,采用PCR扩增后用Sanger法对患者ATP7B基因外显子/内含子连接区进行序列分析。结果:50例WD患者根据临床症状分为肝型14例、脑型28例和其他型8例。50例WD患者中ATP7B基因变异结果:纯合子3例,复合杂合子32例和单一杂合突变13例,三处杂合突变1例,四处杂合子突变1例。共检测到30种不同的ATP7B基因突变,突变频率比较高的为p.Arg778Leu,p.Pro992Leu,p.Ala874Val,p.Arg919Trp,p.Val1106Ile。结论:本研究发现肝型WD患者发病早期主要表现为转氨酶升高,血清铜蓝蛋白降低,且以幼儿为主。p.Arg778Leu和p.Pro992Leu为ATP7B基因常见的突变,共发现30种ATP7B基因突变,为WD的早期确诊、家系筛查及产前诊断提供科学依据。

Objective:To analyze the clinical characteristics and ATP7B gene mutations of Wilson disease(WD)patients in some regions of northern China.Methods:A total of 50 WD patients diagnosed in Zhengzhou Yihe Hospital affiliated to Henan University from November 2018 to April 2022 were selected as the research objects.Peripheral blood genomic DNA was extracted from the patients.After PCR amplification,the sequence of ATP7B gene exon/intron junction region was analyzed by Sanger method.Results:All 50 WD patients had varying degrees of elevated transaminase,liver injury symptoms,and decreased ceruloplasmin.According to the clinical symptoms,there were 14 cases of hepatic type,28 cases of cerebral type and 8 cases of other types.Among the 50 WD patients,the ATP7B gene mutation results were homozygous in 3 cases,compound heterozygous in 32 cases and single heterozygous in 13 cases,heterozygous in 3 cases and heterozygous in 4 cases.Detected a total of 30 different ATP7B gene mutations,for p.Arg778Leu mutation frequency is higher,Pro992Leu,p.Ala874Val,p.Arg919Trp,p.Val1106Ile.Conclusion:This study found that the early onset of hepatic type WD patients mainly showed elevated transaminase and decreased serum ceruloplasmin,mainly in young children.p.Arg778Leu and p.Pro992Leu are common mutations of ATP7B gene.A total of 30 ATP7B gene mutations have been found,which provide scientific basis for early diagnosis of WD.