1例早发脑型肝豆状核变性家系ATP7B基因突变和临床表型分析  

Identification of pathogenic variations in a Chinese pedigress affected with Wilson’s disease

作　　者：钱南南 王久香 裴培[3] 杨悦 杨文明[3] QIAN Nannan;WANG Jiuxiang;PEI Pei(Clinical Research and Experimental Center of the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine,Hefei 230031,China)

机构地区：[1]安徽中医药大学研究生院,安徽合肥230038 [2]安徽中医药大学第一附属医院临床研究实验中心,安徽合肥230031 [3]安徽中医药大学第一附属医院脑病科,安徽合肥230031

出　　处：《中风与神经疾病杂志》2021年第11期1016-1019,共4页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金(81703109);国家自然科学基金(81803903);国家自然科学基金(81973825);国家中医药脑病循证能力提升及平台建设项目(2019XZZX-NB001);安徽中医药大学自然科学基金(2017zryb020);安徽中医药大学新安医学教育部重点实验室开放基金(2020xayx12)。

摘　　要：目的探讨1例早发脑型肝豆状核变性家系的临床表型和遗传学病因。方法提取该家系先证者及其父母和弟弟的外周白细胞基因组DNA,用Sanger法对先证者ATP7B基因外显子及外显子/内含子连接区进行序列分析,并对先证者的弟弟进行突变位点检测。结果该家系先证者主要临床特征是记忆力减退,言语不清,肢体不自主抖动,角膜K-F环(+),肝功能正常。Sanger测序显示先证者ATP7B基因第8和第13外显子分别存在c.2333G>T(p.Arg>Leu)、c.2975C>T(p.Pro>Leu)复合杂合错义变异。两种变异均为已知致病突变,分别来自母亲和父亲。先证者弟弟携带c.2333G>T(p.Arg>Leu),目前表型正常。结论该家系为ATP7B基因突变导致的脑型Wilson病。ATP7B基因c.2333G>T(p.Arg>Leu)和c.2975C>T(p.Pro>Leu)是该家系患病的遗传学病因,对家系中的后代再发风险有重要的指导意义。Objective To determine the mutational characterization of P-type ATP7B gene in a Chinese family with neurological Wilson disease(WD).Methods Genomic DNA was isolated from venous blood samples of all available family members.The exons and exon-intron boundaries of ATP7B in four members were analyzed by Sanger sequencing.Results The proband was presented with memory loss,unclear speech and involuntary shaking,k-f ring with normal liver function.By direct Sanger sequencing of ATP7B,the proband have carried two heterozygous missense mutations c.2333G>T p.R778L and c.2975C>T p.P992 L,which were derived her mother and father respectively.The younger brother of the proband carried c.2333G>T p.R778L with nomal presentation.Conclusion We identified two heterozygous missense mutations(c.2120A>G p.Q707R and c.2333G>T p.R778L)were this neurological WD causative sites,which have important guiding significance for the risk of offspring recurrence in this family.

关 键 词：肝豆状核变性 ATP7B 脑型 

分 类 号：R742.4[医药卫生—神经病学与精神病学]