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DOI: 10.1055/a-2468-5250
Case Report

Whole-exome sequencing identifies novel mutation in intrahepatic cholestasis of pregnancy: A case report and literature review

Xixi Deng
1   Department of Obstetrics and Gynecology, Sichuan University West China Second University Hospital, Chengdu, China (Ringgold ID: RIN198150)
2   Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University West China Second University Hospital, Chengdu, China (Ringgold ID: RIN645647)
,
Xueqi Li
1   Department of Obstetrics and Gynecology, Sichuan University West China Second University Hospital, Chengdu, China (Ringgold ID: RIN198150)
2   Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University West China Second University Hospital, Chengdu, China (Ringgold ID: RIN645647)
,
Yongchi Zhan
1   Department of Obstetrics and Gynecology, Sichuan University West China Second University Hospital, Chengdu, China (Ringgold ID: RIN198150)
2   Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University West China Second University Hospital, Chengdu, China (Ringgold ID: RIN645647)
,
Yuxin Ren
1   Department of Obstetrics and Gynecology, Sichuan University West China Second University Hospital, Chengdu, China (Ringgold ID: RIN198150)
2   Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University West China Second University Hospital, Chengdu, China (Ringgold ID: RIN645647)
,
Tingting Xu‡
1   Department of Obstetrics and Gynecology, Sichuan University West China Second University Hospital, Chengdu, China (Ringgold ID: RIN198150)
2   Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University West China Second University Hospital, Chengdu, China (Ringgold ID: RIN645647)
,
Xiaodong Wang  ‡
1   Department of Obstetrics and Gynecology, Sichuan University West China Second University Hospital, Chengdu, China (Ringgold ID: RIN198150)
2   Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University West China Second University Hospital, Chengdu, China (Ringgold ID: RIN645647)
› InstitutsangabenGefördert durch: Key Research and Development Project by Department of Science and Technology in Sichuan Province 2022YFS0042
Gefördert durch: National Natural Science Foundation for Young Scientists of China 82001560
Gefördert durch: Science Foundation for Young Scientists of Sichuan Province 2023NSFSC1608
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Abstract

Objective

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease characterized by pruritus and elevated total bile acid (TBA) levels. The most serious impact of ICP is sudden unexplained intrauterine fetal death, especially when an associated TBA ≥ 100 µmol/L is confirmed.

Methods

We report a case of a 27-year-old female patient with early-onset severe refractory ICP. Whole-exome sequencing and mutation analyses were performed to obtain genetic data on the patient and her mother. Sanger sequencing was performed to screen the mutation site. Computer-based algorithms were applied to predict the pathogenesis of the identified mutation. Subsequently, we conducted a literature review to characterize the pathological features and perinatal management of severe refractory ICP, especially ICP with genetic susceptibility.

Results

A heterozygous mutation in the ABCD3 gene: c.130C > T/p.Pro44Ser was detected in this patient. Through the analysis of pathogenicity prediction software, the mutations were disease-causing. This is the first report to identify the novel p.Pro44Ser mutations of ABCD3 gene in ICP patients.

Conclusions

Our report provides new insights into the genetic architecture of ICP involving ABCD3 variants. Early-onset severe refractory ICP is rare and mutations in bile acid metabolism genes might accentuate the phenotype. Emphasized perinatal management and screening for potential pathogenicity sites of variants that drive specific recognition of ICP is necessary.

Keywords

intrahepatic cholestasis of pregnancy - bile acids - ABCD3 - ursodeoxycholic acid - mutation

Supplementary Material



Publikationsverlauf

Eingereicht: 19. September 2024

Angenommen nach Revision: 31. Oktober 2024

Artikel online veröffentlicht:
15. Januar 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

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