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Nat Genet. 2014 Apr;46(4):326-8. doi: 10.1038/ng.2918. Epub 2014 Mar 9.

Mutations in TJP2 cause progressive cholestatic liver disease.

Author information

1
Institute of Liver Studies, Division of Transplantation Immunology and Mucosal Biology, King's College London School of Medicine, London, UK.
2
Institute of Liver Studies, King's College Hospital, London, UK.
3
Biomedical Research Centre (BRC) Genomics Core Facility, Guy's and St Thomas' National Health Service (NHS) Foundation Trust and King's College London, London, UK.
4
King's College Hospital NHS Foundation Trust, Department of Haematological Medicine, London, UK.
5
Leeds Institute of Molecular Medicine, St James's University Hospital, University of Leeds, Leeds, UK.
6
Renal Sciences, Division of Transplantation Immunology and Mucosal Biology, King's College London School of Medicine, London, UK.
7
1] Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada. [2] Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
8
1] Institute of Liver Studies, Division of Transplantation Immunology and Mucosal Biology, King's College London School of Medicine, London, UK. [2] Paediatric Liver, GI and Nutrition Centre, King's College Hospital, London, UK.
9
Histopathology Department, Royal Hallamshire Hospital, Sheffield, UK.
10
Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, USA.
11
Department of Pediatrics, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, Colorado, USA.
12
Department of Genome Sciences, University of Washington, Seattle, Washington, USA.
13
Children's Liver and Gastroenterology Unit, Leeds General Infirmary, Leeds, UK.
14
Division of Genetics and Molecular Medicine, King's College London School of Medicine, Guy's Hospital, London, UK.
15
1] Liver Center Laboratory, Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.

Abstract

Elucidating genetic causes of cholestasis has proved to be important in understanding the physiology and pathophysiology of the liver. Here we show that protein-truncating mutations in the tight junction protein 2 gene (TJP2) cause failure of protein localization and disruption of tight-junction structure, leading to severe cholestatic liver disease. These findings contrast with those in the embryonic-lethal knockout mouse, highlighting differences in redundancy in junctional complexes between organs and species.

PMID:
24614073
PMCID:
PMC4061468
DOI:
10.1038/ng.2918
[Indexed for MEDLINE]
Free PMC Article

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