儿童肝豆状核变性的临床资料与ATP7B基因分析

Clinical characteristics and ATP7B gene analysis of 158 children with Wilson’s disease

目的 分析肝豆状核变性(WD)患儿的临床资料及ATP7B基因变异特点。方法 收集2016年1月至2022年6月于西安交通大学附属儿童医院感染科就诊的158例WD患儿的临床资料,根据受累器官及临床表现的不同,分为肝型WD(n=144)和脑型WD(n=14)。根据肝脏受累的轻重程度及病程长短、表现的差异,肝型WD又分为症状前WD(n=114)、急慢性肝炎型WD(n=30)。采用目标基因捕获、高通量测序技术进行基因检测,根据是否存在c.2333G>T(p.R778L)变异,分为R778L型(n=55)与其他型WD组(n=61)。比较各组间患儿的一般情况、临床表现及实验室指标。结果 症状前WD患儿的确诊年龄小于急慢性肝炎型WD与脑型WD(Z值分别为-56.640、-64.956,P<0.05);急慢性肝炎型WD患儿的病程短于症状前WD患儿(Z=26.930,P<0.05)。ATP7B基因热点突变前4位依次为c.2333G>T(等位基因频率为28.88%)、c.2621C>T(等位基因频率为9.48%)、c.2310C>G(等位基因频率为8.62%)及c.2975C>T(等位基因频率为7.76%)。R778L组WD患儿的确诊年龄大于其他型WD(Z=2.082,P<0.05)。结论 儿童WD以肝脏表现常见,基因型与临床表型无明显相关性。

Objective To explore the clinical characteristics and ATP7B gene of patients with Wilson’s disease(WD).Methods The clinical data were collected in 158 cases of WD children who were admitted to the Department of Infectious Diseases in Xi'an Jiaotong University Affiliated Children's Hospital from January 2016 to June 2022.According to the different affected organs and clinical manifestations,it is divided into liver subtype WD(n=144)and neurological subtype WD(n=14).According to the severity and duration of liver involvement,as well as differences in symptoms,liver type WD can be divided into pre symptom WD(n=114)and acute and chronic hepatitis type WD(n=30).Gene detection was performed by target gene capture and high-throughput sequencing technology.According to the presence of c.2333G>T(p.R778L)variant,it was divided into R778L group(n=55)and other groups(n=61).The general conditions,clinical manifestations and laboratory examination indexes were compared among the groups.Results The age of diagnosis of presymptomatic WD was lower than acute or chronic hepatitis and neurological subtype WD(Z values are-56.640 and-64.956,respectively,P<0.05),the course of acute or chronic hepatitis WD was shorter than that of presymptomatic WD(Z=26.930,P<0.05),and there was no difference in sex among the three groups(P>0.05).The first four hot spot mutations of ATP7B gene were c.2333G>T(28.9%of alleles),c.2621C>T(9.5%of alleles),c.2310C>G(8.6%of alleles)and c.2975C>T(7.8%of alleles).The age of diagnosis of WD in R778L group was higher than that of other types of WD(Z=2.082,P<0.05).Conclusions The liver manifestation is common in children with WD,and there is no significant correlation between genotype and clinical phenotype.