{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:30:36Z","timestamp":1792467036608,"version":"4.5.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T00:00:00Z","timestamp":1640304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015034","name":"Resist","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015034","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>NF-\u03baB1 deficiency is suggested to be the most common cause of common variable immunodeficiency (CVID). <jats:italic>NFKB1<\/jats:italic> encodes for the p105 precursor protein of NF-\u03baB1, which is converted into the active transcriptional subunit p50 through proteasomal processing of its C-terminal half upon stimulation and is implicated in the canonical NF-kB pathway. Rare monoallelic <jats:italic>NFKB1<\/jats:italic> variants have been shown to cause (haplo) insufficiency. Our report describes a novel <jats:italic>NFKB1<\/jats:italic> missense variant (c.691C&amp;gt;T, p.R230C; allele frequency 0.00004953) in a family vulnerable to meningitis, sepsis, and late-onset hypogammaglobulinemia. We investigated the pathogenic relevance of this variant by lymphocyte stimulation, immunophenotyping, overexpression study and immunoblotting. The ectopic expression of p50 for c.691 C&amp;gt;T restricted transcriptionally active p50 in the cytoplasm, and immunoblotting revealed reduced p105\/50 expression. This study shows that the deleterious missense variant in NFKB1 adversely affects the transcriptional and translational activity of NF\u03baB1, impairing its function. Patients immunological parameters show a progressive course of hypogammaglobulinemia, which may partially account for the incomplete disease penetrance and suggest the need for closer immunological monitoring of those mutation carriers.<\/jats:p>","DOI":"10.3389\/fimmu.2021.767188","type":"journal-article","created":{"date-parts":[[2021,12,24]],"date-time":"2021-12-24T04:46:02Z","timestamp":1640321162000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Vulnerability to Meningococcal Disease in Immunodeficiency Due to a Novel Pathogenic Missense Variant in 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