75例肝型肝豆状核变性患儿的临床表型及ATP7B基因变异分析  

Analysis of clinical phenotypes and ATP7B gene variants in 75 children patients with Wilson’s disease

作　　者：刘攀 车凤玉 舒畅 李亚绒[1] 刘小乖[1] Liu Pan;Che Fengyu;Shu Chang;Li Yarong;Liu Xiaoguai(Department of Infectious Disease,Xi’an Children’s Hospital,Xi’an,Shaanxi 710003,China;Institute of Pediatric Diseases of Shaanxi Province,Xi’an Children’s Hospital,Xi’an,Shaanxi 710003,China)

机构地区：[1]西安市儿童医院感染科,西安710003 [2]西安市儿童医院陕西省儿童疾病研究所,西安710003

出　　处：《中华医学遗传学杂志》2022年第4期357-361,共5页Chinese Journal of Medical Genetics

基　　金：西安市卫生健康委员会研究项目(2021yb30);西安市儿童医院项目(2020D02)。

摘　　要：目的分析西北地区肝型肝豆状核变性(Wilson’s disease,WD)患儿的临床特征与ATP7B基因变异情况。方法回顾分析75例肝型WD患儿的临床及ATP7B基因变异的特点。结果75例患儿中,症状前患儿4例,表现为单纯转氨酶升高者59例,急慢性肝病者12例;ATP7B基因纯合变异9例,复合杂合变异64例,杂合变异2例;共检测出49个变异,高发变异位点为c.2333G>T(p.Arg778Leu)、c.2621C>T(p.Ala874Val)及c.2975C>T(Pro992Leu),等位基因频率分别为28.7%、12.7%及9.3%;检出了c.1908dupC(p.Asn637Glnfs*118)、c.4179_4180insC(p.Pro1394Profs*15)、c.1604A>G(p.Glu535Gly)、c.2278C>T(p.Pro760Ser)、c.3008C>A(p.Ala1003Glu)及c.3532A>C(p.Thr1178Pro)6个新变异,除c.1604A>G(p.Glu535Gly)为临床意义不明确变异外,余均为可能致病性变异。儿童肝型WD的基因型-表型间无明显相关性。结论西北地区肝型WD患儿常见ATP7B变异类型为c.2333G>T(p.Arg778Leu)、c.2621C>T(p.Ala874Val)及c.2975C>T(p.Pro992Leu),基因型-表型间无明显相关性。Objective To analyze the clinical phenotypes and ATP7B gene variants among children patients with Wilson’s disease from Northwestern China.Methods The clinical features and variants of the ATP7B gene among 75 children with hepatic Wilson’s disease were retrospectively analyzed.Results Among the 75 cases,4 were presymptomatic,59 had isolated transaminase elevation,12 had acute and/or chronic liver diseases.Nine children were found to harbor homozygous variants,64 harbored compound heterozygous variants,and two only had heterozygous variants of the ATP7B gene.In total 49 variants were detected,with common variants including c.2333G>T(p.Arg778Leu),c.2621C>T(p.Ala874Val)and c.2975C>T(Pro992Leu),which yielded allelic frequencies of 28.7%,12.7%and 9.3%,respectively.Six novel variants were detected,which included c.1908dupC(p.Asn637Glnfs*118),c.4179_4180insC(p.Pro1394Profs*15),c.1604A>G(p.Glu535Gly),c.2278C>T(p.Pro760Ser),c.3008C>A(p.Ala1003Glu)and c.3532A>C(p.Thr1178Pro).Except for c.1604A>G(p.Glu535Gly),the remainder five were all predicted to be likely pathogenic.No significant correlation was found between genotype and phenotype among the patients.Conclusion The common mutation types of the ATP7B gene among patients with hepatic Wilson disease in Northwestern China are c.2333G>T(p.Arg778Leu),c.2621C>T(p.Ala874Val)and c.2975C>T(p.Pro992Leu),there is no significant correlation between their genotypes and phenotypes.

关 键 词：儿童 肝豆状核变性 ATP7B基因 基因变异 

分 类 号：R742.4[医药卫生—神经病学与精神病学]