2. Academic Validation
  3. Mutations in TJP2 cause progressive cholestatic liver disease

Mutations in TJP2 cause progressive cholestatic liver disease

  • Nat Genet. 2014 Apr;46(4):326-8. doi: 10.1038/ng.2918.
Melissa Sambrotta 1,  Sandra Strautnieks 2,  Efterpi Papouli 3,  Peter Rushton 4,  Barnaby E Clark 4,  David A Parry 5,  Clare V Logan 5,  Lucy J Newbury 6,  Binita M Kamath 7,  Simon Ling 7,  Tassos Grammatikopoulos 8,  Bart E Wagner 9,  John C Magee 10,  Ronald J Sokol 11,  Giorgina Mieli-Vergani 8,  University of Washington Center for Mendelian Genomics,  Joshua D Smith 12,  Colin A Johnson 5,  Patricia McClean 13,  Michael A Simpson 14,  A S Knisely 2,  Laura N Bull 15,  Richard J Thompson 8
Affiliations

Affiliations

  • 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.
PMID: 24614073 DOI: 10.1038/ng.2918
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.

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