进行性家族性肝内胆汁淤积症2例临床及遗传学分析

Clinical and genetic analysis of two cases with progressive familial intrahepatic cholestasis

目的探讨进行性家族性肝内胆汁淤积症(PFIC)的临床及遗传学特征。方法回顾分析2例PFIC患儿的临床资料和基因检测结果。结果例1,女性,15岁,临床表现以黄疸、皮肤瘙痒、白色黏稠便为主,伴脾大;例2,男性,3岁6月龄,表现为黄疸、皮肤瘙痒。全外显子测序发现,例1的ATP8B1基因存在c.2652G>C和c.1573C>T复合杂合变异,其中c.2652G>C变异遗传自父亲,c.1573C>T变异遗传自母亲,c.2652G>C是既往未见报道的新变异位点。例2的ABCB11基因存在c.2606A>C纯合错义变异,来源于父母。结论基因检测有助于PFIC的明确诊断及治疗。此研究丰富了ATP8B1致病变异谱。

Objective To explore the clinical and genetic characteristics of progressive familial intrahepatic cholestasis(PFIC).Method Clinical data and genetic results of the patients were retrospectively analyzed.Peripheral blood samples were collected,and genomic DNA was extracted,whole exome sequencing(WES)was used to identify the genetic cause.Results Case 1,a 15 years old female,presented with jaundice,skin itching,white sticky stools,accompanied by splenomegaly;case 2,a 3 years and 6 months old male,manifested as jaundice and skin itching.WES analysis revealed compound heterozygous mutations of c.2652G>C from the father and c.1573C>T from the mother in the ATP8B1 gene of patient 1.c.2652 G>C is a novel mutation which has not been reported before.In case 2,WES identified a homozygous missense mutation of c.2606 A>C in the ABCB11 gene,which were inherited from his parents.Conclusion The diagnosis of progressive familial intrahepatic cholestasis needs to combine clinical manifestations,histopathological findings and genetic testing,and to exclude other related diseases that lead to cholestasis;genetic testing is helpful for confirming the diagnosis and treatment of PFIC.The mutations reported in this paper enriched the pathogenic mutation spectrum of ATP8B1.