【摘要】 目的 通过第二代DNA测序技术，对以“头部不自主抖动”为首发症状的成人肝豆状核变性患者家系内ATP7B致病基因特点及候选突变位点进行分析，探讨错义和同义突变的临床意义。方法 采用第二代DNA测序技术，检测先证者及其家系其他成员ATP7B基因序列。结果 先证者ATP7B基因存在Exon8 c.2333G>T p.(Arg778Leu)错义杂合突变、Exon14 c.3243G>A p.(Glu1081=)同义杂合突变(参考序列NM＿000053.3),其小妹存在相同突变；先证者女儿基因检测提示：Exon14 c.3243G>A p.(Glu1081=)同义杂合突变(参考序列NM＿000053.3),其儿子及大妹存在相同突变位点；患者母亲基因检测提示：Exon8 c.2333G>T p.(Arg778Leu)错义杂合突变，与患者弟弟存在相同突变；生物信息学分析结果表明，突变位点c.2333G>T p.(Arg778Leu)致病，并同时存在c.3243G>A p.(Glu1081=)同义突变。结论 c.3243G>A同义突变影响mRNA的剪接，导致外显子跳跃，进一步丰富了同义突变的临床意义。通过肝豆状核变性家系内基因筛查，可为早期诊断、治疗及预防提供依据。更多还原

【Abstract】 Objective To analyze the characteristics of ATP7 B pathogenic genes in the family of adult patients with hepatolenticular degeneration with “head involuntary shaking” as the first symptom and to conduct bioinformatics analysis of candidate mutation sites, and to explore the relationship between missense and synonymous mutations clinical significance.Methods The ATP7 B gene sequence of an adult proband with hepatolenticular degeneration and other members of the family were detected by using second-generation DNA sequencing technology.Results Proband ATP7 B gene Exon8 c.2333 G>T p.(Arg778 Leu) missense heterozygous mutation, Exon 14 c.3243 G>A p.(Glu1081=) had synonymous heterozygous mutation(Reference sequence NM＿000053.3),his younger sister had the same mutation; The genetic test of the daughter of the proband suggested that: Exon 14 c.3243 G>A(P.Glu1081=) synonymous heterozygous mutation.(Reference sequence NM＿000053.3),his son and eider sister had the same mutation site. The genetic test of patient’s mother revealed that Exon8 c.2333 G>T p.(Arg778 Leu) missense heterozygous mutation, which had the same mutation in the patient’s brother; The results of bioinformatics analysis indicated that the causative mutation site was c.2333 G>T p.(Arg778 Leu),and there was a synonymous mutations on c.3243 G>A(P.Glu1081=) at the same time.Conclusion c.3243 G>A synonymous mutations could affect mRNA splicing, leading to exon skipping, which further enriches the clinical significance of synonymous mutations. Gene screening in families with hepatolenticular degeneration can provide the basis for early diagnosis, treatment and prevention.更多还原