实用肝脏病杂志2024，Vol.27Issue(2)：218-221,4.DOI:10.3969/j.issn.1672-5069.2024.02.015
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
摘要
Abstract
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 in41 alleles,with33.1%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)were found with 4.8%,3.2%and 3.2%allelic frequencies;34 missense mutations,15 insertion mutations,8 shear mutations and 5 nonsense mutations were detected in our series and there were compound heterozygosity in 45 cases,heterozygosity mutation in 7 cases and homozygous mutation in 10 cases;there was no statistical differences as respect to the mutation frequencies of the top five pathogenic mutation genes,e.g.,p.Arg778Le,p.Pro992Leu,p.Ala874Val,IvS4-5:t＞g and p.Glu332stop between children with liver illness and neuropathy phenotypes(P＞0.05).Conclusion The common clinical phenotype of children with WD is liver involvement,and the top five pathogenic gene variants are Arg778Leu,Pro992Leu,Ala874Val,Ala874Val and Glu332stop,which might be firstly sequenced for early diagnosis,but the gene screening probably hard to predict the clinical phenotypes.关键词
肝豆状核变性/临床表型/ATP7B/基因突变谱/儿童Key words
Wilson's disease/Clinical phenotypes/ATP7B/Gene mutation profile/Children引用本文复制引用
严盼盼,黄晓霞,祝峰,滕懿群,杨露露..肝豆状核变性儿童临床表型与ATP7B基因突变谱变化研究[J].实用肝脏病杂志,2024,27(2):218-221,4.基金项目
浙江省嘉兴市科技计划项目(编号:2021AD30089) （编号:2021AD30089）
