{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T11:01:09Z","timestamp":1776423669300,"version":"3.51.2"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T00:00:00Z","timestamp":1727913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israeli Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Personal Research Grant","award":["3115\/19"],"award-info":[{"award-number":["3115\/19"]}]},{"name":"Kronitz Family Sheba Research-Scientist Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Inborn errors of immunity (IEI) are a large heterogeneous group of diseases characterized by immunodeficiency, immune dysregulation, allergy, auto-inflammation, and predisposition to malignancies. Most are inherited as an autosomal recessive trait. We studied a patient with severe combined immunodeficiency (SCID) and immune dysregulation who harbored two distinct biallelic IEI-associated genetic mutations. Clinical, immunological, and genetic data were collected. Genetic investigation included whole-exome sequencing on DNA extracted from skin fibroblasts. Family segregation was performed by Sanger sequencing. Immunological evaluation included absolute and functional evaluations of lymphocytes and chimerism analysis post-hematopoietic stem cell transplantation (HSCT). Treg subsets, lipopolysaccharide-responsive and beige-like anchor (LRBA), and Cytotoxic T-Lymphocyte Associated protein 4 (CTLA4) expression levels were measured by flow cytometric analysis. A 19-year-old female patient from a consanguineous background underwent unconditioned matched sibling-related HSCT during infancy due to the clinical presentation of SCID with an Omenn phenotype. At that time, her underlying genetic defect was not defined. Years after HSCT, severe autoimmune phenomena were noted, including a systemic lupus erythematosus-like syndrome and ophthalmic manifestations. Genetic evaluation revealed biallelic homozygous mutations in recombination activating gene-2 (c.685C&amp;gt;T, p.Arg229Trp) and a previously undescribed mutation in LRBA (c.3325G&amp;gt;T, p.Asp1109Tyr). LRBA and CTLA4 expression levels were normal, suggesting that the LRBA variant identified in these kindred is unlikely to be pathogenic. Multiple genetic defects causing complex IEIs may be identified in the same individual in highly consanguineous populations. Functional immunological testing is essential for the evaluation of novel genetic variants.<\/jats:p>","DOI":"10.1093\/cei\/uxae083","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T15:18:31Z","timestamp":1727882311000},"source":"Crossref","is-referenced-by-count":2,"title":["Investigating concomitant\n                    <i>RAG-2<\/i>\n                    and\n                    <i>LRBA<\/i>\n                    mutations in SCID and autoimmunity"],"prefix":"10.1093","volume":"220","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5950-7437","authenticated-orcid":false,"given":"Ilia","family":"Spivak","sequence":"first","affiliation":[{"name":"Clinical Immunology, Angioedema and Allergy Institute, The Center for Autoimmune Diseases, Sheba Medical Center , Tel Hashomer ,","place":["Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shirly","family":"Frizinsky","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Tel Aviv University , Tel Aviv ,","place":["Israel"]},{"name":"Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center , Tel HaShomer ,","place":["Israel"]},{"name":"Cancer Research Center, Pediatric Immunology Unit, Jeffrey Modell Foundation (JMF) Center, Department of Pediatrics, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center , Tel Hashomer ,","place":["Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amarilla","family":"Mandola","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Tel Aviv University , Tel Aviv ,","place":["Israel"]},{"name":"Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center , Tel HaShomer ,","place":["Israel"]},{"name":"Cancer Research Center, Pediatric Immunology Unit, Jeffrey Modell Foundation (JMF) Center, Department of Pediatrics, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center , Tel Hashomer ,","place":["Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atar","family":"Lev","sequence":"additional","affiliation":[{"name":"Cancer Research Center, Pediatric Immunology Unit, Jeffrey Modell Foundation (JMF) Center, Department of Pediatrics, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center , Tel Hashomer ,","place":["Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amos J","family":"Simon","sequence":"additional","affiliation":[{"name":"Cancer Research Center, Pediatric Immunology Unit, Jeffrey Modell Foundation (JMF) Center, Department of Pediatrics, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center , Tel Hashomer ,","place":["Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ortal","family":"Barel","sequence":"additional","affiliation":[{"name":"The Genomic Unit, Sheba Cancer Research Center, Sheba Medical Center , Tel Hashomer ,","place":["Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicktoria","family":"Vishnevskia-Dai","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Tel Aviv University , Tel Aviv ,","place":["Israel"]},{"name":"Ocular Oncology Service, The Goldschleger Eye Institute, Sheba Medical Center , Tel HaShomer ,","place":["Israel"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raz","family":"Somech","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Tel Aviv University , Tel Aviv ,","place":["Israel"]},{"name":"Pediatric Department A and Immunology Service, Jeffrey Modell Foundation Center, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center , Tel HaShomer ,","place":["Israel"]},{"name":"Cancer Research Center, Pediatric Immunology Unit, Jeffrey Modell Foundation (JMF) Center, Department of Pediatrics, Edmond and Lily 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