{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:38:30Z","timestamp":1789054710292,"version":"build-2803163510"},"reference-count":80,"publisher":"American Society of Hematology","issue":"17","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,10,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The discovery of humans with monogenic disorders has a rich history of generating new insights into biology. Here we report the first human identified with complete deficiency of nuclear factor of activated T cells 1 (NFAT1). NFAT1, encoded by NFATC2, mediates calcium-calcineurin signals that drive cell activation, proliferation, and survival. The patient is homozygous for a damaging germline NFATC2 variant (c.2023_2026delTACC; p.Tyr675Thrfs\u221718) and presented with joint contractures, osteochondromas, and recurrent B-cell lymphoma. Absence of NFAT1 protein in chondrocytes caused enrichment in prosurvival and inflammatory genes. Systematic single-cell\u2013omic analyses in PBMCs revealed an environment that promotes lymphomagenesis with accumulation of na\u00efve B cells (enriched for oncogenic signatures MYC and JAK1), exhausted CD4+ T cells, impaired T follicular helper cells, and aberrant CD8+ T cells. This work highlights the pleiotropic role of human NFAT1, will empower the diagnosis of additional patients with NFAT1 deficiency, and further defines the detrimental effects associated with long-term use of calcineurin inhibitors.<\/jats:p>","DOI":"10.1182\/blood.2022015674","type":"journal-article","created":{"date-parts":[[2022,7,5]],"date-time":"2022-07-05T16:11:48Z","timestamp":1657037508000},"page":"1858-1874","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":17,"title":["Human complete NFAT1 deficiency causes a triad of\u00a0joint contractures, osteochondromas, and B-cell\u00a0malignancy"],"prefix":"10.1182","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9591-0415","authenticated-orcid":false,"given":"Mehul","family":"Sharma","sequence":"first","affiliation":[{"name":"1Department of Pediatrics, BC Children\u2019s Hospital, The University of British Columbia, Vancouver, BC, 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