AUTHOR=Cheng Jinlin , Gong Ling , Mi Xiaoxiao , Wu Xiangyan , Zheng Jun , Yang Wenjun 

TITLE=Case series of progressive familial intrahepatic cholestasis type 3: Characterization of variants in ABCB4 in China

JOURNAL=Frontiers in Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.962408

DOI=10.3389/fmed.2022.962408

ISSN=2296-858X

ABSTRACT=Objective: To improve the accuracy of the diagnosis of familial progressive intrahepatic cholestasis type 3 (PFIC3, https://www.omim.org/entry/602347)
Method: Between September 2019 and March 2021, we recruited four patients with PFIC3 from two liver centers in East China. Molecular genetic findings of ATP-binding cassette subfamily B member 4 (ABCB4, https://www.omim.org/entry/171060) were prospectively examined, and clinical records, laboratory readouts, and macroscopic and microscopic appearances of the liver were analyzed. 
Results: Four patients experienced cholestasis, mild jaundice, and elevated levels of serum direct bilirubin, γ-glutamyltransferase, or total bile acids. All patients had moderate-to-severe liver fibrosis or biliary cirrhosis, and their liver biopsy specimens stained positive with rhodamine. Molecular immunohistochemistry revealed reduced or absent MDR3 expression in all liver specimens. A novel mutation of ABCB4 (c.1560+2T>A) was identified in patients with PFIC3, which is of high clinical significance and may help understand mutant ABCB4 pathogenesis. 
Conclusions: MDR3 immunohistochemistry and molecular genetic analyses of ABCB4 are essential for the accurate diagnosis of PFIC3.