Caspar I van der Made, Simone Kersten, Odelia Chorin, Karin R Engelhardt, Gayatri Ramakrishnan, Helen Griffin, Ina Schim van der Loeff, Hanka Venselaar, Annick Raas Rothschild, Meirav Segev, Janneke H M Schuurs-Hoeijmakers, Tuomo Mantere, Rick Essers, Masoud Zamani Esteki, Amir L Avital, Peh Sun Loo, Annet Simons, Rolph Pfundt, Adilia Warris, Marieke M Seyger, Frank L van de Veerdonk, Mihai G Netea, Mary A Slatter, Terry Flood, Andrew R Gennery, Amos J Simon, Atar Lev, Shirley Frizinsky, Ortal Barel, Mirjam van der Burg, Raz Somech, Sophie Hambleton, Stefanie S V Henriet, Alexander Hoischen
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...
March 12, 2024: American Journal of Human Genetics