{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:50:53Z","timestamp":1787946653802,"version":"build-2784847793"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,12,26]],"date-time":"2022-12-26T00:00:00Z","timestamp":1672012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"State Key Clinical Specialty of China for Hematological Diseases"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170124"],"award-info":[{"award-number":["82170124"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rongxiang Regenerative Medicine Foundation of Shandong University","award":["2019SDRX-02"],"award-info":[{"award-number":["2019SDRX-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Common variable immunodeficiency (CVID) is a \u2018late-onset\u2019 primary immunodeficiency characterized by variable manifestations and genetic heterogeneity. A monogenic cause of CVID has been reported in 10% of patients. In this study, we identified two novel pathogenic variants implicated in monogenic CVID by whole exome sequencing (WES) analysis: a heterozygous nuclear factor \u03baB subunit 1 (NFKB1) p.G686fs mutation and a homozygous inducible T-cell co-stimulator (ICOS) p.L96Sfs mutation. The predicted crystal models indicated premature truncation of the two mutated proteins. Both variants were demonstrated as loss-of-function mutations and were associated with overlapped manifestations of respiratory fungal infection and splenomegaly. We further performed a detailed assessment of immunologic phenotypes and impaired lymphocyte functions in patients. Moreover, we discovered an association between monoclonal T-large granular lymphocyte proliferation and ICOS-deficient CVID for the first time. These observations lead to a new perspective on the underlying genetic heterogeneity of CVID.<\/jats:p>","DOI":"10.1093\/cei\/uxac121","type":"journal-article","created":{"date-parts":[[2022,12,26]],"date-time":"2022-12-26T10:41:10Z","timestamp":1672051270000},"page":"68-77","source":"Crossref","is-referenced-by-count":5,"title":["Identification of novel NFKB1 and ICOS frameshift variants in patients with CVID"],"prefix":"10.1093","volume":"211","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5543-5819","authenticated-orcid":false,"given":"Anli","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University , Jinan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University , Jinan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoqiu","family":"Leng","sequence":"additional","affiliation":[{"name":"Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University , Jinan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University , Jinan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University , Jinan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Hematology, Qilu Hospital, Cheeloo College of Medicine, Shandong University , Jinan , 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