Identification of eight novel proteasome variants in five unrelated cases of proteasome-associated autoinflammatory syndromes (PRAAS)
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). Pa...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-08-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1190104/full |
| _version_ | 1797754659535847424 |
|---|---|
| author | Jonas Johannes Papendorf Frédéric Ebstein Sara Alehashemi Daniela Gerent Petry Piotto Anna Kozlova Maria Teresa Terreri Anna Shcherbina Andre Rastegar Marta Rodrigues Renan Pereira Sophia Park Bin Lin Kat Uss Sophie Möller Ana Flávia da Silva Pina Flavio Sztajnbok Sofia Torreggiani Julie Niemela Jennifer Stoddard Sergio D. Rosenzweig Andrew J. Oler Colton McNinch Marietta M. de Guzman Adriana Fonseca Nicole Micheloni Melissa Mariti Fraga Sandro Félix Perazzio Raphaela Goldbach-Mansky Adriana A. de Jesus Elke Krüger |
| author_facet | Jonas Johannes Papendorf Frédéric Ebstein Sara Alehashemi Daniela Gerent Petry Piotto Anna Kozlova Maria Teresa Terreri Anna Shcherbina Andre Rastegar Marta Rodrigues Renan Pereira Sophia Park Bin Lin Kat Uss Sophie Möller Ana Flávia da Silva Pina Flavio Sztajnbok Sofia Torreggiani Julie Niemela Jennifer Stoddard Sergio D. Rosenzweig Andrew J. Oler Colton McNinch Marietta M. de Guzman Adriana Fonseca Nicole Micheloni Melissa Mariti Fraga Sandro Félix Perazzio Raphaela Goldbach-Mansky Adriana A. de Jesus Elke Krüger |
| author_sort | Jonas Johannes Papendorf |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T17:35:36Z |
| format | Article |
| id | doaj.art-797414f038e44fa0bb0b536c59ac957d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T17:35:36Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-797414f038e44fa0bb0b536c59ac957d2023-08-04T11:18:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.11901041190104Identification of eight novel proteasome variants in five unrelated cases of proteasome-associated autoinflammatory syndromes (PRAAS)Jonas Johannes Papendorf0Frédéric Ebstein1Sara Alehashemi2Daniela Gerent Petry Piotto3Anna Kozlova4Maria Teresa Terreri5Anna Shcherbina6Andre Rastegar7Marta Rodrigues8Renan Pereira9Sophia Park10Bin Lin11Kat Uss12Sophie Möller13Ana Flávia da Silva Pina14Flavio Sztajnbok15Sofia Torreggiani16Julie Niemela17Jennifer Stoddard18Sergio D. Rosenzweig19Andrew J. Oler20Colton McNinch21Marietta M. de Guzman22Adriana Fonseca23Nicole Micheloni24Melissa Mariti Fraga25Sandro Félix Perazzio26Raphaela Goldbach-Mansky27Adriana A. de Jesus28Elke Krüger29Institut für Medizinische Biochemie und Molekularbiologie (IMBM), Universitätsmedizin Greifswald, Greifswald, GermanyInstitut für Medizinische Biochemie und Molekularbiologie (IMBM), Universitätsmedizin Greifswald, Greifswald, GermanyTranslational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesDivision of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (Unifesp), São Paulo, BrazilDepartment of Immunology, D.Rogachev National Medical and Research Center for Pediatric Hematology, Oncology, and Immunology, Moscow, RussiaDivision of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (Unifesp), São Paulo, BrazilDepartment of Immunology, D.Rogachev National Medical and Research Center for Pediatric Hematology, Oncology, and Immunology, Moscow, RussiaTranslational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesDivision of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilDepartment of Pediatrics, Universidade Federal de Ciencias da Saude de Porto Alegre, Porto Alegre, BrazilTranslational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesTranslational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesTranslational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesInstitut für Medizinische Biochemie und Molekularbiologie (IMBM), Universitätsmedizin Greifswald, Greifswald, GermanyDivision of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (Unifesp), São Paulo, BrazilDivision of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilTranslational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesImmunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United StatesImmunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United StatesImmunology Service, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United StatesBioinformatics 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 StatesBioinformatics 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 StatesSection of Pediatric Rheumatology, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX, United StatesDivision of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, BrazilDivision of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (Unifesp), São Paulo, BrazilDivision of Pediatric Rheumatology, Department of Pediatrics, Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil0Division of Rheumatology – Department of Medicine, Universidade Federal de São Paulo (Unifesp), Sao Paulo, BrazilTranslational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesTranslational Autoinflammatory Diseases Section (TADS), Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesInstitut für Medizinische Biochemie und Molekularbiologie (IMBM), Universitätsmedizin Greifswald, Greifswald, GermanyMutations 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1190104/fullproteasomopathyproteasome associated autoinflammatory syndrometype I interferoninterferonopathyPSMB8PSMB10 |
| spellingShingle | Jonas Johannes Papendorf Frédéric Ebstein Sara Alehashemi Daniela Gerent Petry Piotto Anna Kozlova Maria Teresa Terreri Anna Shcherbina Andre Rastegar Marta Rodrigues Renan Pereira Sophia Park Bin Lin Kat Uss Sophie Möller Ana Flávia da Silva Pina Flavio Sztajnbok Sofia Torreggiani Julie Niemela Jennifer Stoddard Sergio D. Rosenzweig Andrew J. Oler Colton McNinch Marietta M. de Guzman Adriana Fonseca Nicole Micheloni Melissa Mariti Fraga Sandro Félix Perazzio Raphaela Goldbach-Mansky Adriana A. de Jesus Elke Krüger Identification of eight novel proteasome variants in five unrelated cases of proteasome-associated autoinflammatory syndromes (PRAAS) Frontiers in Immunology proteasomopathy proteasome associated autoinflammatory syndrome type I interferon interferonopathy PSMB8 PSMB10 |
| title | Identification of eight novel proteasome variants in five unrelated cases of proteasome-associated autoinflammatory syndromes (PRAAS) |
| title_full | Identification of eight novel proteasome variants in five unrelated cases of proteasome-associated autoinflammatory syndromes (PRAAS) |
| title_fullStr | Identification of eight novel proteasome variants in five unrelated cases of proteasome-associated autoinflammatory syndromes (PRAAS) |
| title_full_unstemmed | Identification of eight novel proteasome variants in five unrelated cases of proteasome-associated autoinflammatory syndromes (PRAAS) |
| title_short | Identification of eight novel proteasome variants in five unrelated cases of proteasome-associated autoinflammatory syndromes (PRAAS) |
| title_sort | identification of eight novel proteasome variants in five unrelated cases of proteasome associated autoinflammatory syndromes praas |
| topic | proteasomopathy proteasome associated autoinflammatory syndrome type I interferon interferonopathy PSMB8 PSMB10 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1190104/full |
| work_keys_str_mv | AT jonasjohannespapendorf identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT fredericebstein identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT saraalehashemi identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT danielagerentpetrypiotto identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT annakozlova identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT mariateresaterreri identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT annashcherbina identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT andrerastegar identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT martarodrigues identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT renanpereira identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT sophiapark identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT binlin identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT katuss identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT sophiemoller identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT anaflaviadasilvapina identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT flaviosztajnbok identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT sofiatorreggiani identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT julieniemela identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT jenniferstoddard identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT sergiodrosenzweig identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT andrewjoler identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT coltonmcninch identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT mariettamdeguzman identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT adrianafonseca identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT nicolemicheloni identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT melissamaritifraga identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT sandrofelixperazzio identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT raphaelagoldbachmansky identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT adrianaadejesus identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas AT elkekruger identificationofeightnovelproteasomevariantsinfiveunrelatedcasesofproteasomeassociatedautoinflammatorysyndromespraas |