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CASE REPORT article

Front. Genet.

Sec. Genetics of Common and Rare Diseases

Case report: mild BRIC-like cholestasis despite a gross USP53 deletion—novel findings and literature review

Provisionally accepted
Ekaterina NuzhnayaEkaterina Nuzhnaya1*Tatiana CherevatovaTatiana Cherevatova1Zhanna MarkovaZhanna Markova1Ekaterina LotnikEkaterina Lotnik1Aleksandra ShagiazdanovaAleksandra Shagiazdanova2Ekaterina FilimonovaEkaterina Filimonova2Olga ParshinaOlga Parshina3Anastasiia A. BuianovaAnastasiia A. Buianova3Anastasia BobreshovaAnastasia Bobreshova1Andrey MarakhonovAndrey Marakhonov1Natalia SemenovaNatalia Semenova1
  • 1Research Centre for Medical Genetics, Moscow, Russia
  • 2Rossijskaa detskaa kliniceskaa bol'nica, Moscow, Russia
  • 3Rossijskij nacional'nyj issledovatel'skij medicinskij universitet imeni N I Pirogova, Moscow, Russia

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We report a pediatric case of cholestatic liver disease associated with two novel compound heterozygous variants in the USP53 gene: a truncating c.1219A>T (p.Lys407*) variant inherited from the father and a maternally inherited gross deletion involving exons 13–19. Despite the disruptive nature of these variants, the patient presented with a benign recurrent intrahepatic cholestasis (BRIC) characterized by episodic pruritus, jaundice and elevated bile acids with preserved liver function between episodes. Liver histology revealed fibrosis with a cholestatic component, consistent with mild progressive familial intrahepatic cholestasis (PFIC) features. Molecular diagnosis was confirmed by whole-exome sequencing (WES), chromosomal microarray, and Sanger sequencing. A systematic review of 39 published cases was conducted, revealing that USP53-related disease exhibits broad clinical variability, ranging from BRIC to PFIC7. Our findings expand the spectrum of USP53 variants, underscore the relevance of large deletions and emphasize the inclusion of USP53 in genetic panels for idiopathic low-gamma-glutamyl transferase (GGT) cholestasis.

Keywords: Usp53, BRIC, PFIC7, low-GGT cholestasis, pediatric hepatology, Gross deletion, compound heterozygous variants

Received: 21 Jul 2025; Accepted: 03 Nov 2025.

Copyright: © 2025 Nuzhnaya, Cherevatova, Markova, Lotnik, Shagiazdanova, Filimonova, Parshina, Buianova, Bobreshova, Marakhonov and Semenova. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Ekaterina Nuzhnaya, nuzhnaya@med-gen.ru

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material