一例进行性家族性肝内胆汁淤积症3型患儿的临床及遗传学分析

Clinical and genetic analysis of a family affected by progressive familial intrahepatic cholestasis type 3

目的探讨1例遗传性胆汁淤积症患儿的临床及遗传学特点。方法收集患儿临床资料，采用外显子组捕获测序检测患儿的致病突变，并进行Sanger测序验证。结果患儿为一名5岁男孩，表现为严重胆汁淤积性肝硬化。基因分析结果显示患儿为ABCB4基因新突变c．1006-2A〉G和c．3580C〉T（p．R1194X）的复合杂合子，突变分别来源于其父母亲；蛋白结构预测分析显示突变c．3580C〉T导致截短型多药耐药蛋白3的形成。结论临床及基因分析明确患儿为进行性家族性肝内胆汁淤积症3型，扩展了ABCB4基因突变谱，为家系遗传咨询和产前诊断提供了依据。

Objective To explore the clinical and genetic characteristics of a family affected by genetic chotestasis. Methods Clinical data of the patient was collected. Targeted exome sequencing was carried out to detect the pathogenic mutations. The results were confirmed by Sanger sequencing. Results The patient, a 5-year-old boy, presented with severe cholestatic cirrhosis. Genetic analysis revealed that he has carried compound heterozygous mutations c. 1006-2A〉G and c. 3580C〉T （p. R1194X） of the ABCB4 gene, which were inherited from his father and mother, respectively. By structural prediction, the mutation c. 3580C〉T can give rise to a truncated multi-drug resistance protein 3 （MDR3）. Conclusion The patient was diagnosed with progressive familial intrahepatic cholestasis type 3 （PFIC-3） based on clinical and molecular findings. Detection of novel mutations of the ABCB4 gene has provided valuable clues for the diagnosis and genetic counseling.