Identification of eight novel proteasome variants in five unrelated cases of proteasome-associated autoinflammatory syndromes (PRAAS).

Autor:	Papendorf JJ; Institut für Medizinische Biochemie und Molekularbiologie (IMBM), Universitätsmedizin Greifswald, Greifswald, Germany., Ebstein F; Institut für Medizinische Biochemie und Molekularbiologie (IMBM), Universitätsmedizin Greifswald, Greifswald, Germany., Alehashemi S; Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States., Piotto DGP; Division of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil., Kozlova A; Department of Immunology, D.Rogachev National Medical and Research Center for Pediatric Hematology, Oncology, and Immunology, Moscow, Russia., Terreri MT; Division of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil., Shcherbina A; Department of Immunology, D.Rogachev National Medical and Research Center for Pediatric Hematology, Oncology, and Immunology, Moscow, Russia., Rastegar A; Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States., Rodrigues M; Division of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil., Pereira R; Department of Pediatrics, Universidade Federal de Ciencias da Saude de Porto Alegre, Porto Alegre, Brazil., Park S; Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States., Lin B; Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States., Uss K; Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States., Möller S; Institut für Medizinische Biochemie und Molekularbiologie (IMBM), Universitätsmedizin Greifswald, Greifswald, Germany., da Silva Pina AF; Division of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil., Sztajnbok F; Division of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil., Torreggiani S; Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States., Niemela J; Immunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United States., Stoddard J; Immunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United States., Rosenzweig SD; Immunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United States., Oler AJ; Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States., McNinch C; Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States., de Guzman MM; Section of Pediatric Rheumatology, Texas Children's Hospital, Baylor College of Medicine, Houston, TX, United States., Fonseca A; Division of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil., Micheloni N; Division of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil., Fraga MM; Division of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil., Perazzio SF; Division of Rheumatology - Department of Medicine, Universidade Federal de São Paulo (Unifesp), Sao Paulo, Brazil., Goldbach-Mansky R; Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States., de Jesus AA; Translational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States., Krüger E; Institut für Medizinische Biochemie und Molekularbiologie (IMBM), Universitätsmedizin Greifswald, Greifswald, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Aug 04; Vol. 14, pp. 1190104. Date of Electronic Publication: 2023 Aug 04 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1190104
Abstrakt:	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, PSMB8 and PSMB10 , whereas one patient showed additive loss-of-function mutations in PSMB8 . Variants in two previously not associated proteasome genes, PSMA5 and PSMC5 , were found in a patient who also carried the PSMB8 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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer SD declared a past co-authorship with the authors FE and EK to the handling editor. (Copyright © 2023 Papendorf, Ebstein, Alehashemi, Piotto, Kozlova, Terreri, Shcherbina, Rastegar, Rodrigues, Pereira, Park, Lin, Uss, Möller, da Silva Pina, Sztajnbok, Torreggiani, Niemela, Stoddard, Rosenzweig, Oler, McNinch, de Guzman, Fonseca, Micheloni, Fraga, Perazzio, Goldbach-Mansky, de Jesus and Krüger.)
Databáze:	MEDLINE
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