{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:40:59Z","timestamp":1793047259525,"version":"4.5.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T00:00:00Z","timestamp":1637020800000},"content-version":"vor","delay-in-days":2199,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Excellence Initiative of the German Research Foundation"},{"name":"German Federal Ministry of Education and Research","award":["01EO0803"],"award-info":[{"award-number":["01EO0803"]}]},{"name":"German Federal Ministry of Education and Research","award":["01GM1111B"],"award-info":[{"award-number":["01GM1111B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,1,13]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>The gene PIK3CD codes for the catalytic subunit of phosphoinositide 3-kinase \u03b4 (PI3K\u03b4), and is expressed solely in leucocytes. Activating mutations of PIK3CD have been described to cause an autosomal dominant immunodeficiency that shares clinical features with common variable immunodeficiency (CVID). We screened a cohort of 669 molecularly undefined primary immunodeficiency patients for five reported mutations (four gain-of-function mutations in PIK3CD and a loss of function mutation in PIK3R1) using pyrosequencing. PIK3CD mutations were identified in three siblings diagnosed with CVID and two sporadic cases with a combined immunodeficiency (CID). The PIK3R1 mutation was not identified in the cohort. Our patients with activated PI3K\u03b4 syndrome (APDS) showed a range of clinical and immunological findings, even within a single family, but shared a reduction in naive T cells. PIK3CD gain of function mutations are more likely to occur in patients with defective B and T cell responses and should be screened for in CVID and CID, but are less likely in patients with a pure B cell\/hypogammaglobulinaemia phenotype.<\/jats:p>","DOI":"10.1111\/cei.12706","type":"journal-article","created":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T07:59:08Z","timestamp":1444118348000},"page":"221-229","source":"Crossref","is-referenced-by-count":91,"title":["Activating PI3K\u03b4 mutations in a cohort of 669 patients with primary immunodeficiency"],"prefix":"10.1093","volume":"183","author":[{"given":"M","family":"Elgizouli","sequence":"first","affiliation":[{"name":"Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany"},{"name":"Faculty of Biology, Albert Ludwigs University, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D M","family":"Lowe","sequence":"additional","affiliation":[{"name":"Institute of Immunity and Transplantation, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Speckmann","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany"},{"name":"Department of Pediatrics and Adolescent Medicine, University Medical Center, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Schubert","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany"},{"name":"Spemann Graduate School of Biology and Medicine (SGBM), Albert Ludwigs University, Freiburg, Germany"},{"name":"Faculty of Biology, Albert Ludwigs University, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"H\u00fclsd\u00fcnker","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany"},{"name":"Spemann Graduate School of Biology and Medicine (SGBM), Albert Ludwigs University, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z","family":"Eskandarian","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Dudek","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany"},{"name":"Spemann Graduate School of Biology and Medicine (SGBM), Albert Ludwigs University, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Schmitt-Graeff","sequence":"additional","affiliation":[{"name":"Department of Pathology, University Medical Center, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Wanders","sequence":"additional","affiliation":[{"name":"Institute of Immunity and Transplantation, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S F","family":"J\u00f8rgensen","sequence":"additional","affiliation":[{"name":"Research Institute of Internal Medicine, Oslo University Hospital and University of Oslo, and Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Fevang","sequence":"additional","affiliation":[{"name":"Research Institute of Internal Medicine, Oslo University Hospital and University of Oslo, and Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U","family":"Salzer","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Nieters","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Burns","sequence":"additional","affiliation":[{"name":"Institute of Immunity and Transplantation, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Grimbacher","sequence":"additional","affiliation":[{"name":"Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freiburg, Germany"},{"name":"Institute of Immunity and Transplantation, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,11,9]]},"reference":[{"key":"2021111804085980200_cei12706-bib-0001","first-page":"162.","article-title":"Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency","volume":"5","author":"Al-Herz","year":"2014","journal-title":"Front Immunol"},{"key":"2021111804085980200_cei12706-bib-0002","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/ni902","article-title":"Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency","volume":"4","author":"Grimbacher","year":"2003","journal-title":"Nat Immunol"},{"key":"2021111804085980200_cei12706-bib-0003","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.1073\/pnas.94.9.4330","article-title":"P110delta, a novel phosphoinositide 3-kinase in 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