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Functional validation revealed aberrant lymphocyte cell states, confirming activated phosphoinositide 3-kinase-\u03b4 syndrome 2 and supporting targeted treatment. This work reinforces the importance of precise genetic diagnosis in primary immunodeficiencies.<\/jats:p>","DOI":"10.70962\/jhi.20250085","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T06:21:12Z","timestamp":1753424472000},"update-policy":"https:\/\/doi.org\/10.70962\/jhi.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Functional validation of\n                    <i>PIK3R1<\/i>\n                    variant causing activated phosphoinositide 3-kinase-\u03b4 syndrome 2 with hypogammaglobulinemia and bronchiectasis"],"prefix":"10.70962","volume":"1","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5437-3456","authenticated-orcid":true,"given":"Marat","family":"Kribis","sequence":"first","affiliation":[{"name":"Yale School of Medicine 1 Department of Immunobiology, , New Haven, CT,","place":["USA"]},{"name":"Yale School of Medicine 2 Department of Medicine, Section of Rheumatology, Allergy and Immunology, , New Haven, CT,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4471-0966","authenticated-orcid":true,"given":"Bradly M.","family":"Bauman","sequence":"additional","affiliation":[{"name":"Yale School of Medicine 1 Department of Immunobiology, , New Haven, CT,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9806-4739","authenticated-orcid":true,"given":"Cullen M.","family":"Dutmer","sequence":"additional","affiliation":[{"name":"Emory University School of Medicine 3 Division of Allergy and Immunology, Department of Pediatrics, , Atlanta, GA,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6334-5266","authenticated-orcid":true,"given":"Jordan","family":"Abbott","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine 4 Department of Pediatrics, Section of Allergy and Immunology, , Aurora, CO,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2630-8882","authenticated-orcid":true,"given":"Jason","family":"Catanzaro","sequence":"additional","affiliation":[{"name":"Kaiser Permanente 5 Department of Allergy and Immunology, , Denver, CO,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5754-0820","authenticated-orcid":true,"given":"Carrie L.","family":"Lucas","sequence":"additional","affiliation":[{"name":"Yale School of Medicine 1 Department of Immunobiology, , New Haven, CT,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"2026041709170401500_bib1","doi-asserted-by":"publisher","first-page":"3923","DOI":"10.1172\/JCI75746","article-title":"A human immunodeficiency caused by mutations in the PIK3R1 gene","volume":"124","author":"Deau","year":"2014","journal-title":"J. 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