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

Jinlin Cheng; Ling Gong; Xiaoxiao Mi; Xiangyan Wu; Jun Zheng; Wenjun Yang

doi:10.3389/fmed.2022.962408

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

Front Med (Lausanne). 2022 Dec 8:9:962408. doi: 10.3389/fmed.2022.962408. eCollection 2022.

Authors

Jinlin Cheng¹, Ling Gong², Xiaoxiao Mi³, Xiangyan Wu⁴, Jun Zheng⁴, Wenjun Yang⁴

Affiliations

¹ State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
² Department of Infectious Diseases, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
³ Department of Translational Medicine Platform, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.
⁴ Department of Pathology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.

Abstract

Objective: To improve the accuracy of the diagnosis of familial progressive intrahepatic cholestasis type 3 (PFIC3, https://www.omim.org/entry/602347).

Materials and methods: 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 [ATP binding cassette transporter A4 (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.

Conclusion: MDR3 immunohistochemistry and molecular genetic analyses of ABCB4 are essential for the accurate diagnosis of PFIC3.

Keywords: ABCB4; MDR3; PFIC; PFIC3; cholestasis.