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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...

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Autores principales: Papendorf, Jonas Johannes, Ebstein, Frédéric, Alehashemi, Sara, Piotto, Daniela Gerent Petry, Kozlova, Anna, Terreri, Maria Teresa, Shcherbina, Anna, Rastegar, Andre, Rodrigues, Marta, Pereira, Renan, Park, Sophia, Lin, Bin, Uss, Kat, Möller, Sophie, da Silva Pina, Ana Flávia, Sztajnbok, Flavio, Torreggiani, Sofia, Niemela, Julie, Stoddard, Jennifer, Rosenzweig, Sergio D., Oler, Andrew J., McNinch, Colton, de Guzman, Marietta M., Fonseca, Adriana, Micheloni, Nicole, Fraga, Melissa Mariti, Perazzio, Sandro Félix, Goldbach-Mansky, Raphaela, de Jesus, Adriana A., Krüger, Elke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10436547/
https://www.ncbi.nlm.nih.gov/pubmed/37600812
http://dx.doi.org/10.3389/fimmu.2023.1190104
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author Papendorf, Jonas Johannes
Ebstein, Frédéric
Alehashemi, Sara
Piotto, Daniela Gerent Petry
Kozlova, Anna
Terreri, Maria Teresa
Shcherbina, Anna
Rastegar, Andre
Rodrigues, Marta
Pereira, Renan
Park, Sophia
Lin, Bin
Uss, Kat
Möller, Sophie
da Silva Pina, Ana Flávia
Sztajnbok, Flavio
Torreggiani, Sofia
Niemela, Julie
Stoddard, Jennifer
Rosenzweig, Sergio D.
Oler, Andrew J.
McNinch, Colton
de Guzman, Marietta M.
Fonseca, Adriana
Micheloni, Nicole
Fraga, Melissa Mariti
Perazzio, Sandro Félix
Goldbach-Mansky, Raphaela
de Jesus, Adriana A.
Krüger, Elke
author_facet Papendorf, Jonas Johannes
Ebstein, Frédéric
Alehashemi, Sara
Piotto, Daniela Gerent Petry
Kozlova, Anna
Terreri, Maria Teresa
Shcherbina, Anna
Rastegar, Andre
Rodrigues, Marta
Pereira, Renan
Park, Sophia
Lin, Bin
Uss, Kat
Möller, Sophie
da Silva Pina, Ana Flávia
Sztajnbok, Flavio
Torreggiani, Sofia
Niemela, Julie
Stoddard, Jennifer
Rosenzweig, Sergio D.
Oler, Andrew J.
McNinch, Colton
de Guzman, Marietta M.
Fonseca, Adriana
Micheloni, Nicole
Fraga, Melissa Mariti
Perazzio, Sandro Félix
Goldbach-Mansky, Raphaela
de Jesus, Adriana A.
Krüger, Elke
author_sort Papendorf, Jonas Johannes
collection PubMed
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.
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spelling pubmed-104365472023-08-19 Identification of eight novel proteasome variants in five unrelated cases of proteasome-associated autoinflammatory syndromes (PRAAS) Papendorf, Jonas Johannes Ebstein, Frédéric Alehashemi, Sara Piotto, Daniela Gerent Petry Kozlova, Anna Terreri, Maria Teresa Shcherbina, Anna Rastegar, Andre Rodrigues, Marta Pereira, Renan Park, Sophia Lin, Bin Uss, Kat Möller, Sophie da Silva Pina, Ana Flávia Sztajnbok, Flavio Torreggiani, Sofia Niemela, Julie Stoddard, Jennifer Rosenzweig, Sergio D. Oler, Andrew J. McNinch, Colton de Guzman, Marietta M. Fonseca, Adriana Micheloni, Nicole Fraga, Melissa Mariti Perazzio, Sandro Félix Goldbach-Mansky, Raphaela de Jesus, Adriana A. Krüger, Elke Front Immunol Immunology 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. Frontiers Media S.A. 2023-08-04 /pmc/articles/PMC10436547/ /pubmed/37600812 http://dx.doi.org/10.3389/fimmu.2023.1190104 Text en 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 https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Papendorf, Jonas Johannes
Ebstein, Frédéric
Alehashemi, Sara
Piotto, Daniela Gerent Petry
Kozlova, Anna
Terreri, Maria Teresa
Shcherbina, Anna
Rastegar, Andre
Rodrigues, Marta
Pereira, Renan
Park, Sophia
Lin, Bin
Uss, Kat
Möller, Sophie
da Silva Pina, Ana Flávia
Sztajnbok, Flavio
Torreggiani, Sofia
Niemela, Julie
Stoddard, Jennifer
Rosenzweig, Sergio D.
Oler, Andrew J.
McNinch, Colton
de Guzman, Marietta M.
Fonseca, Adriana
Micheloni, Nicole
Fraga, Melissa Mariti
Perazzio, Sandro Félix
Goldbach-Mansky, Raphaela
de Jesus, Adriana A.
Krüger, Elke
Identification of eight novel proteasome variants in five unrelated cases of proteasome-associated autoinflammatory syndromes (PRAAS)
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 Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10436547/
https://www.ncbi.nlm.nih.gov/pubmed/37600812
http://dx.doi.org/10.3389/fimmu.2023.1190104
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