{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T03:35:56Z","timestamp":1777001756972,"version":"3.51.4"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":38,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Pharming Healthcare Inc"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Allergy Asthma Clin Immunol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Activated phosphoinositide 3-kinase \u03b4 syndrome (APDS) is an inborn error of immunity in the\n                      <jats:italic>PIK3CD<\/jats:italic>\n                      gene caused by an increase in phosphoinositide 3-kinase \u03b4 (PI3K\u03b4) activity. APDS is characterized by immune dysregulation such as senescent T cells, lymphoproliferation, and hypogammaglobulinemia. Patients present with lymphoid hyperplasia, recurrent sinopulmonary infections, recurrent viremias, and lymphomas.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We present a case report of a patient with APDS due to a novel variant in the\n                      <jats:italic>PIK3CD<\/jats:italic>\n                      gene. Our patient was identified at 3 years of age due to persistent EBV viremia and Hodgkin lymphoma. Immune evaluation demonstrated upregulation of T follicular helper cells and CD10\u2009+\u2009B cells were consistent with the lymphocytic phenotype present in patients with APDS. However, there was no upregulation of the T cell mTOR pathway by functional testing. The patient was found to carry a novel variant, (c.58G\u2009&gt;\u2009A p.(Val20lle)), in the\n                      <jats:italic>PIK3CD<\/jats:italic>\n                      gene.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We describe a 3-year-old patient with a novel variant in the\n                      <jats:italic>PIK3CD<\/jats:italic>\n                      gene (c.58G\u2009&gt;\u2009A p.(Val20lle)) presenting with EBV viremia, Hodgkin lymphoma, upregulation T follicular helper cells and CD10\u2009+\u2009B cells consistent with a phenotype of APDS in a 3-year-old boy. This case broadens our understanding of the genetic and phenotypic spectrum of\n                      <jats:italic>PIK3CD<\/jats:italic>\n                      gene mutations in APDS.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13223-026-01014-4","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T13:11:37Z","timestamp":1773753097000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["APDS in a 3-year-old boy presenting with EBV viremia and hodgkin lymphoma associated with a novel germline heterozygous variant in PIK3CD and with characteristic immune phenotype but no upregulation of the T cell mTOR pathway"],"prefix":"10.1186","volume":"22","author":[{"given":"Devyani","family":"Bakshi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Wong-Pack","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacey","family":"Marjerrison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rae","family":"Brager","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manish J.","family":"Butte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy J.","family":"Thauland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny","family":"Garkaby","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"issue":"1","key":"1014_CR1","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.gendis.2019.09.015","volume":"7","author":"A Singh","year":"2020","unstructured":"Singh A, Joshi V, Jindal AK, Mathew B, Rawat A. 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