biostudies-literaturevan der Made CIEuropean Research CouncilWellcome Trust791-804https://www.ebi.ac.uk/biostudies/studies/S-EPMC11023912biostudies-literatureUnknown111(4)Mutations in proteasome β-subunits or their chaperone and regulatory proteins are associated with proteasome-associated autoinflammatory disorders (PRAAS). We studied six unrelated infants with three de novo heterozygous missense variants in PSMB10, encoding the proteasome β2i-subunit. Individuals presented with T-B-NK± severe combined immunodeficiency (SCID) and clinical features suggestive of Omenn syndrome, including diarrhea, alopecia, and desquamating erythematous rash. Remaining T cells had limited T cell receptor repertoires, a skewed memory phenotype, and an elevated CD4/CD8 ratio. Bone marrow examination indicated severely impaired B cell maturation with limited V(D)J recombination. All infants received an allogeneic stem cell transplant and exhibited a variety of severe inflammatAmerican journal of human geneticsExpanding the PRAAS spectrum: De novo mutations of immunoproteasome subunit β-type 10 in six infants with SCID-Omenn syndrome.PMC11023912310372Lev ASimons AGriffin HGennery ARLoo PSEsteki MZSegev Mvan de Veerdonk FLSchuurs-Hoeijmakers JHMKersten SEssers RPfundt RSimon AJSchim van der Loeff IAvital ALEngelhardt KRSlatter MAMantere TFrizinsky SFlood TVenselaar HNetea MGBarel OHenriet SSVChorin ORothschild ARRamakrishnan GSeyger MMvan der Burg MHambleton Svan der Made CIHoischen AWarris ASomech RfalseExpanding the PRAAS spectrum: De novo mutations of immunoproteasome subunit β-type 10 in six infants with SCID-Omenn syndrome.Mutations in proteasome β-subunits or their chaperone and regulatory proteins are associated with proteasome-associated autoinflammatory disorders (PRAAS). We studied six unrelated infants with three de novo heterozygous missense variants in PSMB10, encoding the proteasome β2i-subunit. Individuals presented with T-B-NK± severe combined immunodeficiency (SCID) and clinical features suggestive of Omenn syndrome, including diarrhea, alopecia, and desquamating erythematous rash. Remaining T cells had limited T cell receptor repertoires, a skewed memory phenotype, and an elevated CD4/CD8 ratio. Bone marrow examination indicated severely impaired B cell maturation with limited V(D)J recombination. All infants received an allogeneic stem cell transplant and exhibited a variety of severe inflammat2024-01-01T00:00:00Z2024 Apr2026-06-01T22:16:06.205Z2025-04-04T00:34:19.961ZS-EPMC110239123850330010.1016/j.ajhg.2024.02.013