肝豆状核变性儿童临床表型与ATP7B基因突变谱变化研究  

Clinical phenotypes and ATP7B gene mutation profile in children with Wilson's disease

作　　者：严盼盼 黄晓霞 祝峰 滕懿群 杨露露 Yan Panpan;Huang Xiaoxia;Zhu Feng(Department of Pediatrics,Bengbu Medical College Graduate School,Bengbu 233030,Anhui Province,China;不详)

机构地区：[1]蚌埠医学院研究生院儿科,安徽省蚌埠市233030 [2]嘉兴市第二医院儿科 [3]浙江中医药大学附属第一医院儿科

出　　处：《实用肝脏病杂志》2024年第2期218-221,共4页Journal of Practical Hepatology

基　　金：浙江省嘉兴市科技计划项目(编号:2021AD30089)。

摘　　要：目的总结肝豆状核变性(WD)儿童临床表型特征及其ATP7B基因突变谱变化。方法2020年1月~2023年1月我院收治的WD患儿62例,其中肝病组41例(临床型11例和亚临床型30例)和神经病组21例(临床型6例和亚临床型15例),采用直接测序法检测外周静脉血ATP7B基因突变谱,登录ATP7B突变数据库,比对突变结果。采用火焰原子吸收光谱法检测24 h尿铜和血清铜蓝蛋白。结果肝病组起病年龄、角膜K-F环发生率、血清谷丙转氨酶和24 h尿铜水平分别为(6.1±2.5)岁、17.0%、(149.6±51.3)U/L和(157.0±25.7)μg,与神经病组【分别为(9.6±2.9)岁、76.1%、(67.1±11.0)U/L和(272.2±30.8)μg】比,差异均具有统计学意义(P<0.05);临床型肝病组起病年龄、角膜K-F环、血清胆汁酸、谷丙转氨酶和24 h尿铜水平分别为(6.8±1.9)岁、54.5%、(158.5±23.6)μmol/L、(279.6±17.5)U/L和(196.6±62.8)μg,与亚临床型肝病组【分别为(5.1±2.3)岁、3.3%、(16.1±4.1)μmol/L、(90.5±12.1)U/L和(118.1±41.0)μg】比,差异均具有统计学意义(P<0.05),临床型神经病组角膜K-F环、血清胆汁酸、谷丙转氨酶和24 h尿铜水平分别为100.0%、(26.8±5.8)μmol/L、(96.7±10.1)U/L和(376.5±48.9)μg,与亚临床型神经病组【分别为66.7%、(14.4±3.2)μmol/L、(48.5±5.2)U/L和(214.7±55.4)μg】比,差异均具有统计学意义(P<0.05);在ATP7B基因突变谱中,c.2333G>T(Arg778Leu)见于41个等位基因,等位频率占比为33.1%,其次为c.2975G>T(Pro992Leu),见于10个等位基因,等位频率占比为8.1%,再次为c.2621C>T(Ala874Val)、c.1708-5t>g(Ala874Val)和c.994G>T(Glu332stop),等位频率占比分别为4.8%、3.2%和3.2%;检测到错义突变34种,插入突变15种,剪切突变8种,无义突变5种;复合杂合突变45例,杂合突变7例,纯合突变10例;肝病组与神经病组前5致病变异基因(p.Arg778Le、p.Pro992Leu、p.Ala874Val、IVS4-5:t>g和p.Glu332stop)突变频率比较无统计学差异(P>0.05)。结论WD儿童以肝脏受累多见,排名前Objective The aim of this study was to investigate the clinical phenotypes and blood ATP7B gene mutation profile changes in children with Wilson's disease(WD).Methods 62 children with WD including hepatic phenotype in 41 cases(clinical phenotypes in 11 cases and subclinical phenotypes in 30 cases)and neuropathy in 21 cases(clinical phenotypes in 6 cases and subclinical phenotypes in 15 cases)were admitted to our hospital between January 2020 and January 2023.The blood ATP7B gene mutation profile was obtained by gene sequencing and the results were compared in ATP7B mutation data bank.24 hour-urine copper and serum ceruloplasmin levels were assayed by flame atomic absorption spectrometry.Results The onset age,incidence of corneal K-F ring,serum alanine aminotransferase(ALT)and 24-hour urinary copper levels in children with hepatic phenotype were(6.1±2.5)yr,17.0%,(149.6±51.3)U/L and(157.0±25.7)μg,significantly different compared to[(9.6±2.9)yr,76.1%,(67.1±11.0)U/L and(272.2±30.8)μg]in those with neuropathy(P<0.05);the onset age,incidence of corneal K-F ring,bile acid,serum ALT and 24-hour urinary copper levels in children with clinical phenotype of liver disease were(6.8±1.9)yr,54.5%,(158.5±23.6)μmol/L,(279.6±17.5)U/L and(196.6±62.8)μg,significantly different compared to[(5.1±2.3)yr,3.3%,(16.1±4.1)μmol/L,(90.5±12.1)U/L and(118.1±41.0)μg]in those with subclinical phenotype of liver diseases(P<0.05),and the incidence of corneal K-F ring,bile acid,serum ALT and 24-hour urinary copper levels in children with clinical neuropathy were 100.0%,(26.8±5.8)μmol/L,(96.7±10.1)U/L and(376.5±48.9)μg,significantly different compared to[66.7%,(14.4±3.2)μmol/L,(48.5±5.2)U/L and(214.7±55.4)μg]in those with subclinical neuropathy(P<0.05);as for the ATP7B gene mutation spectrum,the c.2333G>T(Arg778Leu)was found in 41 alleles,with 33.1%of allele frequency,the c.2975G>T(Pro992Leu)was found in 10 alleles,with 8.1%of allele frequency,and the C.2621C>T(Ala874Val),c.1708-5t>g(Ala874Val)and c.994G>T(Glu332stop)we

关 键 词：肝豆状核变性 临床表型 ATP7B 基因突变谱 儿童 

分 类 号：R742.4[医药卫生—神经病学与精神病学]