{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:46:57Z","timestamp":1792522017690,"version":"4.5.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Mutations in genes coding for proteasome subunits and\/or proteasome assembly helpers typically cause recurring autoinflammation referred to as chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperatures (CANDLE) or proteasome-associated autoinflammatory syndrome (PRAAS). Patients with CANDLE\/PRAAS present with mostly chronically elevated type I interferon scores that emerge as a consequence of increased proteotoxic stress by mechanisms that are not fully understood. Here, we report on five unrelated patients with CANDLE\/PRAAS carrying novel inherited proteasome missense and\/or nonsense variants. Four patients were compound heterozygous for novel pathogenic variants in the known CANDLE\/PRAAS associated genes, <jats:italic>PSMB8<\/jats:italic> and <jats:italic>PSMB10<\/jats:italic>, whereas one patient showed additive loss-of-function mutations in <jats:italic>PSMB8<\/jats:italic>. Variants in two previously not associated proteasome genes, <jats:italic>PSMA5<\/jats:italic> and <jats:italic>PSMC5<\/jats:italic>, were found in a patient who also carried the <jats:italic>PSMB8<\/jats:italic> founder mutation, p.T75M. All newly identified mutations substantially impact the steady-state expression of the affected proteasome subunits and\/or their incorporation into mature 26S proteasomes. Our observations expand the spectrum of PRAAS-associated genetic variants and improve a molecular diagnosis and genetic counseling of patients with sterile autoinflammation.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1190104","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T11:18:52Z","timestamp":1691147932000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":44,"title":["Identification of eight novel proteasome variants in five unrelated cases of proteasome-associated autoinflammatory syndromes (PRAAS)"],"prefix":"10.3389","volume":"14","author":[{"given":"Jonas 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