Dubin-Johnson综合征临床及遗传学特征（附3例报告）

Clinical and genetic characteristics of three patients with Dubin-Johnson syndrome:A report of 3 cases

目的分析Dubin-Johnson综合征(DJS)临床特点及实验室检查并进行相关文献复习,以提高对该类遗传性疾病的认识,减少误诊。方法2012年10月至2017年10月就诊于广州市妇女儿童医疗中心感染科3例临床疑诊DJS患儿,采用安捷伦外显子芯片捕获+高通量测序的方法对其及父母进行全基因医学外显子测序,分析总结其临床特点及实验室检查并进行相关文献复习。结果3例患儿均为男性,婴儿期起病,一般情况良好,其中1例合并Bartter综合征,表现为反复低钾、无力;3例肝功能均提示总胆红素升高,直接胆红素升高为主,其余酶学指标均正常。基因学检测提示ABCC2上发现基因突变(共5处),均为未见报道的新发突变。结论DJS临床表现轻微无特异性,仅表现为结合胆红素增高,由于缺乏血清学标记物,诊断较为困难。基因学检测可精确诊断,并可进行家系分析及验证,新发突变丰富了ABCC2基因突变谱。

Objective To summarize and analyze the clinical features and laboratory tests of 3 confirmed cases and review relevant literature to improve the understanding of this type of hereditary diseases,reduce misdiagnosis.Methods The clinical characteristics and laboratory examinations of 3 children diagnosed with Dubin-Johnson(DJS)syndrome between October2012 and October 2017 in Guangzhou Women and Children’s Medical Center were analyzed.The whole-genome medical exon sequencing was carried out using Agilent exon chip capture+high-throughput sequencing.The literature was reviewed.Results All the three children were male.The onset was in infancy,the general condition was good,and the growth and development were normal.The liver function of the three cases all indicated that the total bilirubin was elevated with the direct bilirubin being the main,and the other enzymatic indicators were all normal.One of them had Bartter syndrome at the same time,which showed repeated hypokalemia and weakness.Five genetic mutations were found in ABCC2 by genetic testing which had not been reported.Conclusion The clinical manifestations of DJS are mild and non-specific,and the diagnosis is difficult due to the lack of serological markers.Blood genetic testing can be accurately diagnose from the genetic level,and it can be analyzed and verified by the family.The newly discovered mutations enrich the mutation spectrum of the ABCC2 gene.