Standing, ASI, Hong, Y, Paisan-Ruiz, C et al. (11 more authors) (2020) TRAP1 chaperone protein mutations and autoinflammation. Life Science Alliance, 3 (2). e201900376. ISSN 2575-1077
Abstract
We identified a consanguineous kindred, of three affected children with severe autoinflammation, resulting in the death of one sibling and allogeneic stem cell transplantation in the other two. All three were homozygous for MEFV p.S208C mutation; however, their phenotype was more severe than previously reported, prompting consideration of an oligogenic autoinflammation model. Further genetic studies revealed homozygous mutations in TRAP1, encoding the mitochondrial/ER resident chaperone protein tumour necrosis factor receptor associated protein 1 (TRAP1). Identification of a fourth, unrelated patient with autoinflammation and compound heterozygous mutation of TRAP1 alone facilitated further functional studies, confirming the importance of this protein as a chaperone of misfolded proteins with loss of function, which may contribute to autoinflammation. Impaired TRAP1 function leads to cellular stress and elevated levels of serum IL-18. This study emphasizes the importance of considering digenic or oligogenic models of disease in particularly severe phenotypes and suggests that autoinflammatory disease might be enhanced by bi-allelic mutations in TRAP1.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 Standing et al. This is an open access article under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Clinical Musculoskeletal Medicine (LIRMM) (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 05 May 2020 12:42 |
Last Modified: | 05 May 2020 12:42 |
Status: | Published |
Publisher: | Life Science Alliance |
Identification Number: | 10.26508/lsa.201900376 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:160261 |
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