{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T22:51:29Z","timestamp":1781304689967,"version":"3.54.1"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Wuhan Municipal Health Commission","award":["WX19C19"],"award-info":[{"award-number":["WX19C19"]}]},{"name":"Wuhan City Health and Family Planning Commission of clinical medical research major project","award":["WX19M03"],"award-info":[{"award-number":["WX19M03"]}]},{"name":"Hubei Province Health and Family Planning Commission of Scientific Research Project","award":["WJ2019H313"],"award-info":[{"award-number":["WJ2019H313"]}]},{"name":"The Construction Project of Clinical Medical Research Center for Neurodevelopment Disorders in Children in Hubei Province","award":["HST2020-19"],"award-info":[{"award-number":["HST2020-19"]}]},{"name":"the Wuhan Children\u2019s Imaging Clinical Medical Research Center","award":["WK2022-38"],"award-info":[{"award-number":["WK2022-38"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Rheumatol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Germline heterozygous gain-of-function (GOF) mutations in the\n                      <jats:italic>PIK3CD<\/jats:italic>\n                      gene lead to a rare primary immunodeficiency disease known as activated phosphoinositide 3-kinase (PI3K) \u03b4 syndrome type 1(APDS1). Affected patients present a spectrum of clinical manifestations, particularly recurrent respiratory infections and lymphoproliferation, increased levels of serum immunoglobulin (Ig) M, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) viremia. Due to highly heterogeneous phenotypes of APDS1, it is very likely that suspected cases may be misdiagnosed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Herein we reported three patients with different clinical presentations but harboring pathogenic variants in\n                      <jats:italic>PIK3CD<\/jats:italic>\n                      gene detected by trio whole-exome sequencing (trio-WES) and confirmed by subsequent Sanger sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Two heterozygous mutations (c.3061G\u2009&gt;\u2009A, p.E1021K and c.1574\u00a0A\u2009&gt;\u2009G, p.E525G) in\n                      <jats:italic>PIK3CD<\/jats:italic>\n                      (NM_005026.3) were identified by whole exome sequencing (WES) in the three patients. One of two patients with the mutation (c.3061G\u2009&gt;\u2009A) presented with abdominal pain and diarrhea as the first symptoms, which was due to intussusception caused by multiple polyps of colon. The patient with mutation (c.1574\u00a0A\u2009&gt;\u2009G) had an anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV)-like clinical manifestations, including multisystemic inflammation, acute nephritic syndrome, and positive perinuclear ANCA (p-ANCA), thus the diagnosis of ANCA-AAV was considered.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study expands the spectrums of clinical phenotype and genotype of APDS, and demonstrates that WES has a high molecular diagnostic yield for patients with immunodeficiency related symptoms, such as respiratory infections, multiple ecchymosis, ANCA-associated vasculitis, multiple ileocecal polyps, hepatosplenomegaly, and lymphoid hyperplasia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>Retrospectively registered.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12969-024-00955-7","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T07:02:44Z","timestamp":1706511764000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Activated phosphoinositide 3-kinase \u03b4 syndrome caused by PIK3CD mutations: expanding the phenotype"],"prefix":"10.1186","volume":"22","author":[{"given":"Peiwei","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huicong","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianhong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiankai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingjie","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hebin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxia","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6275-1219","authenticated-orcid":false,"given":"Xuelian","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,29]]},"reference":[{"issue":"6160","key":"955_CR1","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1126\/science.1243292","volume":"342","author":"I Angulo","year":"2013","unstructured":"Angulo I, Vadas O, Gar\u00e7on F, et al. 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Written informed consent was obtained from individual or guardian participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors approve of the manuscript\u2019s submission.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"24"}}