CAJ | 학술논문

目的：探讨进行性家族性肝内胆汁淤积症2型（PFIC2）临床特点和基因诊断的临床意义。方法采用多聚酶链反应（PCR）和DNA直接测序方法，检测6例疑似PFIC2患儿编码胆盐输出泵（BEPS）蛋白ABCB11基因的27个外显子，新发现的突变用SIFT、PolyPhen-2、SNPs&GO软件进行致病性预测；回顾性分析患儿的临床资料。结果共检测到4种致病基因突变：p.R928*、p.E554K、p.R575Q、p.Y337H，其中后3种为新发现的突变；经预测3种新发现的突变均可导致疾病。最终2例患儿符合PFIC2基因诊断。2例患儿均于出生1个月内发病，表现为黄疸，肝脾肿大，偶有烦躁不安。血清总胆红素水平升高，并以直接胆红素为主，γ谷酰转肽酶（GGT）<100 U/L，总胆汁酸升高。结论基因诊断有助确诊PFIC2。
목적：탐토진행성가족성간내담즙어적증2형（PFIC2）림상특점화기인진단적림상의의。방법채용다취매련반응（PCR）화DNA직접측서방법，검측6례의사PFIC2환인편마담염수출빙（BEPS）단백ABCB11기인적27개외현자，신발현적돌변용SIFT、PolyPhen-2、SNPs&GO연건진행치병성예측；회고성분석환인적림상자료。결과공검측도4충치병기인돌변：p.R928*、p.E554K、p.R575Q、p.Y337H，기중후3충위신발현적돌변；경예측3충신발현적돌변균가도치질병。최종2례환인부합PFIC2기인진단。2례환인균우출생1개월내발병，표현위황달，간비종대，우유번조불안。혈청총담홍소수평승고，병이직접담홍소위주，γ곡선전태매（GGT）<100 U/L，총담즙산승고。결론기인진단유조학진PFIC2。
Objectives To investigate the clinical features of progressive familial intrahepatic cholestasis type 2 (PFIC2) and to illustrate the importance of genetic diagnosis. Methods The mutations in 27 exons of ABCB11 encoding bile salt export pump (BSEP) were identiifed using polymerase chain reaction (PCR) and direct DNA sequencing in 6 children with suspected PFIC2. The pathogenicity of the newly identiifed mutations were predicted by SIFT, PolyPhen-2, SNPs&GO software. The clini-cal features and laboratory examinations were reviewed. Results Four disease-causing mutations, p.R928*, p.E554K, p.R575Q and p.Y337H were identiifed, and the last three mutations were novel. These three kinds of novel mutations can cause the disease. Two children with genetic diagnosis had such manifestations as onset within a month after birth, jaundice, hepatosplenomegaly, upset, increased levels of total bilirubin and direct bilirubin, GGT<100 U/L and high levels of total bile acid. Conclusions Genetic diagnosis is a potent tool for clinical diagnosis of PFIC2.