{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:07:49Z","timestamp":1788840469450,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T00:00:00Z","timestamp":1784419200000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82302055"],"award-info":[{"award-number":["82302055"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Allergy Immunology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>BCL10 is a core CBM (CARD\u2010BCL10\u2010MALT1) complex component required for antigen receptor\u2010mediated NF\u2010\u03baB activation. BCL10 deficiency is an exceptionally rare autosomal recessive combined immunodeficiency, with only six patients reported to date. We aimed to characterize the clinical, immunologic, and molecular features of a novel homozygous BCL10 variant and explore mechanisms associated with its leaky phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical\/immunologic phenotyping, whole\u2010exome and Sanger sequencing, transcript and protein studies, signaling, cytokine, and T cell proliferation assays, and scRNA\u2010seq were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A novel homozygous BCL10 c.345_346dup (p.Gly116GlufsTer3) variant was identified in a patient with combined immunodeficiency and immune dysregulation, with relatively mild infections, terminal effector\u2010skewed lymphocytes, and partial Treg preservation. In PBMCs, the variant reduced full\u2010length BCL10 transcripts and BCL10 protein while increasing N\u2010terminal transcripts; HEK293T overexpression showed that the mutant construct could produce a low\u2010abundance truncated protein in\u00a0vitro. NF\u2010\u03baB signaling was stimulus dependent, with near\u2010absent p\u2010p65 induction in T cells after PMA\/ionomycin but relative preservation or enhancement after TNF\u2010\u03b1 or LPS. T cell proliferation was partially preserved with anti\u2010CD3\/CD28 but nearly absent with anti\u2010CD3 alone. ScRNA\u2010seq revealed aberrant Treg\u2010associated gene expression, increased activation\/apoptosis\/senescence programs in T and NK cells, enhanced inflammatory signaling in B cells and monocytes, and enrichment of AP\u20101\/MAPK, inflammatory NF\u2010\u03baB, and IFN\u2010response pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This novel linker\u2010region truncating BCL10 variant was associated with leaky combined immunodeficiency with immune dysregulation. Defective CBM\u2010dependent NF\u2010\u03baB activation coexisted with secondary activation of CBM\u2010independent inflammatory and AP\u20101\/MAPK\u2010related programs, suggesting that inflammatory remodeling may contribute to the nonclassical phenotype.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/pai70441-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/pai.70441","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T04:33:27Z","timestamp":1784522007000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A novel linker region truncating variant in\n                    <scp>BCL<\/scp>\n                    10 underlies a leaky immunodeficiency phenotype"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1102-7327","authenticated-orcid":false,"given":"Lin","family":"Tong","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Children and Adolescents' Health and Diseases, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity  Chongqing 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