Mutations in TJP2 cause progressive cholestatic liver disease

Melissa Sambrotta; Sandra Strautnieks; Efterpi Papouli; Peter Rushton; Barnaby E Clark; David A Parry; Clare V Logan; Lucy J Newbury; Binita M Kamath; Simon Ling; Tassos Grammatikopoulos; Bart E Wagner; John C Magee; Ronald J Sokol; Giorgina Mieli-Vergani; Joshua D Smith; Colin A Johnson; Patricia McClean; Michael A Simpson; A S Knisely; Laura N Bull; Richard J Thompson

doi:10.1038/ng.2918

Mutations in TJP2 cause progressive cholestatic liver disease

Melissa Sambrotta, Sandra Strautnieks, Efterpi Papouli, Peter Rushton, Barnaby E Clark, David A Parry, Clare V Logan, Lucy J Newbury, Binita M Kamath, Simon Ling, Tassos Grammatikopoulos, Bart E Wagner, John C Magee, Ronald J Sokol, Giorgina Mieli-Vergani, Joshua D Smith, Colin A Johnson, Patricia McClean, Michael A Simpson, A S KniselyLaura N Bull, Richard J Thompson

Research output: Contribution to journal › Article › peer-review

226 Citations (Scopus)

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.

Original language	English
Pages (from-to)	326-328
Number of pages	3
Journal	Nature Genetics
Volume	46
Issue number	4
Early online date	9 Mar 2014
DOIs	https://doi.org/10.1038/ng.2918
Publication status	Published - 1 Apr 2014

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Sambrotta, M., Strautnieks, S., Papouli, E., Rushton, P., Clark, B. E., Parry, D. A., Logan, C. V., Newbury, L. J., Kamath, B. M., Ling, S., Grammatikopoulos, T., Wagner, B. E., Magee, J. C., Sokol, R. J., Mieli-Vergani, G., Smith, J. D., Johnson, C. A., McClean, P., Simpson, M. A., ... Thompson, R. J. (2014). Mutations in TJP2 cause progressive cholestatic liver disease. Nature Genetics, 46(4), 326-328. https://doi.org/10.1038/ng.2918

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title = "Mutations in TJP2 cause progressive cholestatic liver disease",

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.",

author = "Melissa Sambrotta and Sandra Strautnieks and Efterpi Papouli and Peter Rushton and Clark, {Barnaby E} and Parry, {David A} and Logan, {Clare V} and Newbury, {Lucy J} and Kamath, {Binita M} and Simon Ling and Tassos Grammatikopoulos and Wagner, {Bart E} and Magee, {John C} and Sokol, {Ronald J} and Giorgina Mieli-Vergani and Smith, {Joshua D} and Johnson, {Colin A} and Patricia McClean and Simpson, {Michael A} and Knisely, {A S} and Bull, {Laura N} and Thompson, {Richard J}",

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Sambrotta, M, Strautnieks, S, Papouli, E, Rushton, P, Clark, BE, Parry, DA, Logan, CV, Newbury, LJ, Kamath, BM, Ling, S, Grammatikopoulos, T, Wagner, BE, Magee, JC, Sokol, RJ, Mieli-Vergani, G, Smith, JD, Johnson, CA, McClean, P, Simpson, MA, Knisely, AS, Bull, LN & Thompson, RJ 2014, 'Mutations in TJP2 cause progressive cholestatic liver disease', Nature Genetics, vol. 46, no. 4, pp. 326-328. https://doi.org/10.1038/ng.2918

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AU - Strautnieks, Sandra

AU - Papouli, Efterpi

AU - Rushton, Peter

AU - Clark, Barnaby E

AU - Parry, David A

AU - Logan, Clare V

AU - Newbury, Lucy J

AU - Kamath, Binita M

AU - Ling, Simon

AU - Grammatikopoulos, Tassos

AU - Wagner, Bart E

AU - Magee, John C

AU - Sokol, Ronald J

AU - Mieli-Vergani, Giorgina

AU - Smith, Joshua D

AU - Johnson, Colin A

AU - McClean, Patricia

AU - Simpson, Michael A

AU - Knisely, A S

AU - Bull, Laura N

AU - Thompson, Richard J

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AB - 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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DO - 10.1038/ng.2918

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SN - 1061-4036

VL - 46

SP - 326

EP - 328

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

Mutations in TJP2 cause progressive cholestatic liver disease

Abstract

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