ArticleArthritis & rheumatology (Hoboken, N.J.)2022
Haploinsufficiency of PSMD12 Causes Proteasome Dysfunction and Subclinical Autoinflammation.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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22 citing papers in PubMed, 29 citations in OpenAlex.
- The ubiquitin-proteasome system and proteostasis in the cochlea and sensorineural hearing disorders.Molecular biomedicine · 2026Review
- Type I Interferonopathies: Fifteen Years On, From Concept to Therapeutic Perspectives.Current rheumatology reports · 2026Review
- PSMD12 Overexpression Promotes Lung Adenocarcinoma Progression via Ubiquitin-Proteasome Pathway Dysregulation.Cancer science · 2026Article
- Molecular mechanisms in rare proteasomopathies.EULAR rheumatology open · 2026Review
- A truncatingFrontiers in immunology · 2026Article
- Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025Review
- PSMD12 promotes hepatocellular carcinoma progression by stabilizing CDK1.Frontiers in immunology · 2025Article
- Understanding neurodevelopmental proteasomopathies as new rare disease entities: A review of current concepts, molecular biomarkers, and perspectives.Genes & diseases · 2024Review
- Nucleotide metabolism, leukodystrophies, and CNS pathology.Journal of inherited metabolic disease · 2024Review
- PSMC5 insufficiency and P320R mutation impair proteasome function.Human molecular genetics · 2024Article
- Modulating the RPS27A/PSMD12/NF-κB pathway to control immune response in mouse brain ischemia-reperfusion injury.Molecular medicine (Cambridge, Mass.) · 2024Article
- Type I interferon pathway in pediatric systemic lupus erythematosus.World journal of pediatrics : WJP · 2024Review
- Proteasome-Associated Syndromes: Updates on Genetics, Clinical Manifestations, Pathogenesis, and Treatment.Journal of clinical immunology · 2024Review
- Expanding the PRAAS spectrum: De novo mutations of immunoproteasome subunit β-type 10 in six infants with SCID-Omenn syndrome.American journal of human genetics · 2024Article
- Proteasome inhibition triggers tissue-specific immune responses against different pathogens in C. elegans.PLoS biology · 2024Article
- Exploring the origins of neurodevelopmental proteasomopathies associated with cardiac malformations: are neural crest cells central to certain pathological mechanisms?Frontiers in cell and developmental biology · 2024Article
- Similarities in the induction of the intracellular pathogen response in Caenorhabditis elegans and the type I interferon response in mammals.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- A gain-of-function variation in PLCG1 causes a new immune dysregulation disease.The Journal of allergy and clinical immunology · 2023Article
- Age-induced alterations of granulopoiesis generate atypical neutrophils that aggravate stroke pathology.Nature immunology · 2023Article
- PSMC3 proteasome subunit variants are associated with neurodevelopmental delay and type I interferon production.Science translational medicine · 2023Article
Corrections and comments
- Erratum issuedErratum.2023
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveProteasome-associated autoinflammatory syndrome (PRAAS) is caused by mutations affecting components of the proteasome and activation of the type I interferon (IFN) pathway. This study was undertaken to investigate the pathogenic mechanisms of a newly recognized type of PRAAS caused by PSMD12 haploinsufficiency.
methodsWhole-exome sequencing was performed in members of a family with skin rash, congenital uveitis, and developmental delay. We performed functional studies to assess proteasome dysfunction and inflammatory signatures in patients, and single-cell RNA sequencing to further explore the spectrum of immune cell activation.
resultsA novel truncated variant in PSMD12 (c.865C>T, p.Arg289*) was identified in 2 family members. The impairment of proteasome function was found in peripheral blood mononuclear cells (PBMCs), as well as in PSMD12-knockdown HEK 293T cell lines. Moreover, we defined the inflammatory signatures in patient PBMCs and found elevated IFN signals, especially in monocytes, by single-cell RNA sequencing.
conclusionThese findings indicate that PSMD12 haploinsufficiency causes a set of inflammation signatures in addition to neurodevelopmental disorders. Our work expands the genotype and phenotype spectrum of PRAAS and suggests a bridge between the almost exclusively inflammatory phenotypes in the majority of PRAAS patients and the almost exclusively neurodevelopmental phenotypes in the previously reported Stankiewicz-Isidor syndrome.
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