Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis
Open accessAbstract
Neonatal cholestasis is a potentially life-threatening condition requiring prompt diagnosis. Mutations in several different genes can cause progressive familial intrahepatic cholestasis, but known genes cannot account for all familial cases. Here we report four individuals from two unrelated families with neonatal cholestasis and mutations in NR1H4, which encodes the farnesoid X receptor (FXR), a bile acid-activated nuclear hormone receptor that regulates bile acid metabolism. Clinical features of severe, persistent NR1H4-related cholestasis include neonatal onset with rapid progression to end-stage liver disease, vitamin K-independent coagulopathy, low-to-normal serum gamma-glutamyl transferase activity, elevated serum alpha-fetoprotein and undetectable liver bile salt export pump (ABCB11) expression. Our findings demonstrate a pivotal function for FXR in bile acid homeostasis and liver protection.
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FXR is a member of the steroid/thyroid hormone receptor family of ligand-activated transcription factors.
“Farnesoid X receptor (FXR) is a member of the steroid/thyroid hormone receptor family of ligand-activated transcription factors (Gomez-Ospina et al., 2016).”
From Bacteroides dorei BDX-01 alleviates DSS-induced experimental colitis in mice by regulating intestinal bile salt hydrolase activity and the FXR-NLRP3 signaling pathway (2023) · cites this paper as Gomez-Ospina et al., 2016
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Self-citation
- Authors
- Gomez-Ospina, N., Potter, C. J., Xiao, R., Manickam, K., Kim, M.-S., Kim, K. H., Shneider, B. L., Picarsic, J. L., Jacobson, T. A., Zhang, J., He, W., Liu, P., Knisely, A. S., Finegold, M. J., Muzny, D. M., Boerwinkle, E., Lupski, J. R., Plon, S. E., Gibbs, R. A., Eng, C. M., Yang, Y., Washington, G. C., Porteus, M. H., Berquist, W. E., Kambham, N., Singh, R. J., Xia, F., Enns, G. M., & Moore, D. D.
- Affiliations
- Nationwide Children's Hospital (US)
- Baylor College of Medicine (US)
- University of Pittsburgh (US)
- University of Graz (AT)
- Stanford Medicine (US)
- Mayo Clinic (US)
- Lucile Packard Children's Hospital (US)
- Corresponding author
- Moore, David D.
- ORCID
- Xiao, Rui
- Manickam, Kandamurugu
- Kim, Kang Ho
- Shneider, Benjamin L.
- Picarsic, Jennifer L.
- Zhang, Jing
- He, Weimin
- Liu, Pengfei
- Finegold, Milton J.
- Muzny, Donna M.
- Boerwinkle, Eric
- Lupski, James R.
- Plon, Sharon E.
- Gibbs, Richard A.
- Eng, Christine M.
- Yang, Yaping
- Porteus, Matthew H.
- Kambham, Neeraja
- Singh, Ravinder J.
- Xia, Fan
- Enns, Gregory M.
- Moore, David D.
- Venue
- Nature Communications
- Published
- 2016-02-18
- Volume
- 7
- Issue
- 1
- Pages
- 10713-10713
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4759630
- OpenAlex
- W2283912536
- Cited by
- 300
- References
- 44
- Citations by year
- 2026: 16 · 2025: 23 · 2024: 29 · 2023: 23 · 2022: 34 · 2021: 36 · 2020: 40 · 2019: 22 · 2018: 34 · 2017: 32 · 2016: 9 · 2015: 1
- FWCI
- 17.62
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Johns Hopkins University
- Baylor-Hopkins Center for Mendelian Genomics
- National Heart, Lung, and Blood Institute
- National Human Genome Research Institute (U54HG006542)
- National Institute of Diabetes and Digestive and Kidney Diseases
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- progressive familial intrahepatic cholestasis, farnesoid X receptor, neonatal cholestasis, bile acid homeostasis, nuclear receptors, ABCB11, end-stage liver disease, alpha-fetoprotein, gamma-glutamyl transferase
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily B, Member 11, Receptor, Farnesoid X-Activated, Bile Acids and Salts, Cholestasis, Intrahepatic, Female, Humans, Male, Mutation, Receptors, Cytoplasmic and Nuclear, ATP-Binding Cassette Transporters, Young Adult
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