| http://purl.uniprot.org/citations/35170849 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35170849 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/35170849 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.org/dc/terms/identifier | "doi:10.15252/emmm.202114901"xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.org/dc/terms/identifier | "doi:10.15252/emmm.202114901"xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Schulz A."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Schulz A."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Schuetz C."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Schuetz C."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Monecke T."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Monecke T."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Moepps B."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Moepps B."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Walczak H."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Walczak H."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Fischer-Posovszky P."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Fischer-Posovszky P."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Niessing D."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Niessing D."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Schwarz K."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Schwarz K."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Gierschik P."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Gierschik P."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Rieser E."xsd:string |
| http://purl.uniprot.org/citations/35170849 | http://purl.uniprot.org/core/author | "Rieser E."xsd:string |