[Clinical and genetic analysis of cases of progressive familial intrahepatic cholestasis type 3].

Objective: To conduct clinical and genetic analysis in two cases of cholestatic liver disease to determine the specific etiology of cholestasis. Methods: Clinical data and the medical histories in family members of two cases were collected. The gene variation was detected by whole-exome sequencing technology. Sanger sequencing validation and bioinformatics analysis were performed on patients and their parents with suspected pathogenic mutations. Results: Whole-exome sequencing showed that the ABCB4 gene of case 1 (a male, 16 years old) had compound heterozygous mutations of c.646C > T from the father and c.927T > A from the mother, while the ABCB4 gene of case 2 (a female, 17 years old) had a compound heterozygous mutation of c.2784-1G > A from the father and c.646C > T from the mother. New mutation sites that had not been previously reported were c.646C > T, c.927T > A, and c.2784-1G > A. Conclusion: In this study, both cases had progressive familial intrahepatic cholestasis type 3 (PFIC-3) caused by ABCB4 gene mutations, and it also enriched the ABCB4 pathogenic variant spectrum. Whole-exome sequencing technology provides a reliable diagnostic tool for etiological analysis.目的： 对2例胆汁淤积性肝病患者进行临床及遗传学分析，明确胆汁淤积的具体病因。 方法： 采集2例患者的临床资料及家系成员的病史，应用全外显子测序技术对患者进行基因变异检测，并对疑似致病性变异的患者及其父母进行Sanger测序验证及生物信息学分析。 结果： 全外显子测序显示，患者1（男，16岁）的ABCB4基因存在源自父亲的c.646C > T和源自母亲的c.927T > A的复合杂合突变；患者2（女，17岁）的ABCB4基因存在源自父亲的c.2784-1G > A和源自母亲的c.646C > T的复合杂合突变。c.646C > T、c.927T > A、c.2784-1G > A均为既往未见报道的新变异位点。 结论： 本研究的2例患者均为ABCB4基因突变引起的3型进行性家族性肝内胆汁淤积症，本研究也丰富了ABCB4的致病变异谱；全外显子组测序技术为病因分析提供了可靠的诊断工具。.