5个肝豆状核变性家系的临床特征及基因突变分析

Clinical characteristics and mutation analysis of 5 pedigrees with Wilson’s Disease

目的了解肝豆状核变性家系ATP7B基因突变特点和临床特征,并探讨其突变与肝豆状核变性发病的关系。方法回顾分析收集5个肝豆状核变性家系成员的临床资料及ATP7B基因检测结果。结果5个家系中的患者均出现不同程度的肝脏损害,甚至部分患者发展为肝衰竭,但均未出现神经系统症状,多数患者存在K-F环及血清铜蓝蛋白降低。ATP7B基因检测发现5例先证者均为复合突变致病,而先证者父母仅携带单一致病突变基因。共检测出7种致病性突变,包括5种错义突变,1种无义突变和1种插入突变,其中c.3087_3088insT(p.G1030Wfs*39)为新发现的插入突变。此外还检测出10种单核苷酸多态性。通过家系基因检测诊断出1例症状前患者。结论本研究中,肝豆状核变形患者多表现为肝脏损害,但临床症状及发病年龄不一,基因检测发现复合杂合突变是ATP7B最常见的突变形式,同时还发现了1种新的ATP7B致病突变。基因测序分析有助于快速诊断肝豆状核变性家系中的症状前患者。

Objective To understand the mutation characteristics and clinical characteristics of ATP7B gene of pedigrees with hepatolenticular degeneration(HLD),which is also called Wilson’s Disease(WD),and to explore the relationship between mutation and the pathogenesis of WD.Methods Peripheral blood samples from 5 members of pedigrees with the WD were collected,genomic DNA was extracted,then we analysed the clinical manifestations and mutations.Results All patients in the 5 pedigrees showed liver damage of varying degrees,and even some patients developed liver failure,but no neurological symptoms occurred.Most patients had K-F ring and with decreased serum ceruloplasmin.ATP7B gene detection showed that all the five probands were caused by multiple mutations,while the parents of the probands only carried a single pathogenic mutation gene.Seven pathogenic mutations were detected,including five missense mutations,one nonsense mutations and one insertion mutation,in which c.3087_3088insT(p.G1030Wfs*39)was a new insertion mutation.In addition,10 single nucleotide polymorphisms were detected.One pre symptomatic patient was diagnosed by family genetic testing.Conclusion In this study,most patients with WD show liver damage,but the clinical symptoms and ages of onset are different.Compound heterozygous mutation is the most popular mutation form of ATP7B,and a novel pathogenic mutation has been identified.Gene sequencing analysis is helpful for rapid diagnosis of pre symptomatic patients in pedigrees with WD.