ArticleEMBO molecular medicine2022
Compound heterozygous variants in OTULIN are associated with fulminant atypical late-onset ORAS.
Article in EMBO molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- C-terminal Fragment Generated by HOIL-1 Cleavage Suppresses Inflammatory Responses of Myeloid Cells to Alleviate Colitis.Theranostics · 2026Article
- Recent variant discoveries and emerging genetic mechanisms in autoinflammatory diseases.Frontiers in immunology · 2026Review
- Human inborn errors of type I interferon-independent intrinsic immunity in nonleukocytic cells.Current opinion in immunology · 2025Review
- Novel genotypes, phenotypes, and triggers in humans with OTULIN haploinsufficiency.Journal of human immunity · 2025Article
- Update on new autoinflammatory disorders from the 2024 Pediatric Rheumatology European Society Congress.Pediatric rheumatology online journal · 2025Review
- Epidemiology, Clinical Data, and Management of Aseptic Abscess Syndrome: Review of Published Cases Outside France.Epidemiologia (Basel, Switzerland) · 2025Review
- Expanding the phenotypic and genetic spectrum of ORAS with novel homozygous variant in OTULIN gene: a case series and literature review.Pediatric rheumatology online journal · 2025Article
- Primary disorders of polyubiquitination: Dual roles in autoinflammation and immunodeficiency.The Journal of experimental medicine · 2025Review
- Failure to Close: An Unexpected Surgical Complication Reveals OTULIN Haploinsufficiency.ACR open rheumatology · 2025Article
- A de novo dominant-negative variant is associated with OTULIN-related autoinflammatory syndrome.The Journal of experimental medicine · 2024Article
- Dominant negative OTULIN-related autoinflammatory syndrome.The Journal of experimental medicine · 2024Article
- Biallelic human SHARPIN loss of function induces autoinflammation and immunodeficiency.Nature immunology · 2024Article
- OTULIN-related conditions: Report of a new case and review of the literature using GenIA.Research square · 2024Article
- OTULIN haploinsufficiency predisposes to environmentally directed inflammation.Frontiers in immunology · 2024Article
- OTULIN deficiency: focus on innate immune system impairment.Frontiers in immunology · 2024Review
- In an experimental myocardial infarction model, L-arginine pre-intervention may exert cardioprotective effects by regulating OTULIN levels and mitochondrial dynamics.Cell stress & chaperones · 2023Article
- Death by TNF: a road to inflammation.Nature reviews. Immunology · 2023Review
- Disorders of ubiquitylation: unchained inflammation.Nature reviews. Rheumatology · 2022Review
- Cell Death-Related Ubiquitin Modifications in Inflammatory Syndromes: From Mice to Men.Biomedicines · 2022Review
- Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin.Science (New York, N.Y.) · 2022Article
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Authors and funding
21 authors at 3 institutions in 2 countries.
Funding
Abstract
Autoinflammatory diseases are a heterogenous group of disorders defined by fever and systemic inflammation suggesting involvement of genes regulating innate immune responses. Patients with homozygous loss-of-function variants in the OTU-deubiquitinase OTULIN suffer from neonatal-onset OTULIN-related autoinflammatory syndrome (ORAS) characterized by fever, panniculitis, diarrhea, and arthritis. Here, we describe an atypical form of ORAS with distinct clinical manifestation of the disease caused by two new compound heterozygous variants (c.258G>A (p.M86I)/c.500G>C (p.W167S)) in the OTULIN gene in a 7-year-old affected by a life-threatening autoinflammatory episode with sterile abscess formation. On the molecular level, we find binding of OTULIN to linear ubiquitin to be compromised by both variants; however, protein stability and catalytic activity is most affected by OTULIN variant p.W167S. These molecular changes together lead to increased levels of linear ubiquitin linkages in patient-derived cells triggering the disease. Our data indicate that the spectrum of ORAS patients is more diverse than previously thought and, thus, supposedly asymptomatic individuals might also be affected. Based on our results, we propose to subdivide the ORAS into classical and atypical entities.
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Registered trials
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