目的 探讨紧密连接蛋白2（TJP 2）基因变异致进行性家族性肝内胆汁淤积症（PFIC）的临床及基因特征。方 法 总结3例因TJP2基因变异致PFIC患儿的临床资料，并复习相关文献。结果 3例患儿中女性1例、男性2例，均为婴 儿期起病；临床以皮肤黄染为主要表现，伴或不伴皮肤瘙痒。血清总胆红素升高，以直接胆红素升高为主，丙氨酸氨基转 移酶、天冬氨酸氨基转移酶、总胆汁酸升高，γ-谷氨酰转肽酶（GGT）正常或稍低，提示低GGT胆汁淤积症。二代基因测 序发现3例患儿均存在TJP 2复合杂合变异，确诊为TJP 2变异引起的PFIC 4。文献复习显示，TJP 2基因变异可引起PFIC、 高胆烷血症、渐进非综合征性耳聋以及近视等儿童疾病。结论 采用基因检测技术确诊3例TJP2基因复合杂合变异引起 的PFIC 4。

Objective To explore the clinical and genetic characteristics of progressive familial intrahepatic cholestasis (PFIC) caused by tight junction protein 2 (TJP 2 ) gene mutation. Method The clinical data of PFIC caused by TJP 2 gene mutation in 3 children were summarized and the relevant literature was reviewed. Results In all 3 children ( 1 girl and 2 boys), the onset was in infancy and jaundice was the main clinical manifestation with or without pruritus. The serum total bilirubin increased, mainly the direct bilirubin. Alanine aminotransferase, aspartate aminotransferase and total bile acid were elevated, and γ-glutamyl transpeptidase (GGT) was normal or slightly low. The changes of above indexes indicated low GGT cholestasis. The second generation gene sequencing showed that there were TJP2 complex heterozygous variants in all the 3 children, and all of them were diagnosed with PFIC 4 caused by TJP2 mutation. Literature review shows that TJP2 gene mutations can cause childhood diseases such as PFIC, hypercholanemia, progressive non-syndromic deafness, and myopia. Conclusion Three cases of PFIC 4 caused by composite heterozygous variation of TJP2 gene were diagnosed by gene detection.