{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:28:17Z","timestamp":1789576097150,"version":"build-2803163510"},"reference-count":78,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T00:00:00Z","timestamp":1719014400000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100016928","name":"Instituto Nacional de Pediatria","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016928","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Allergy Immunology"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    LRBA is a cytoplasmic protein that is ubiquitously distributed. Almost all LRBA domains have a scaffolding function. In 2012, it was reported that homozygous variants in\n                    <jats:italic>LRBA<\/jats:italic>\n                    are associated with early\u2010onset hypogammaglobulinemia. Since its discovery, more than 100 pathogenic variants have been reported. This review focuses on the variants reported in\n                    <jats:italic>LRBA<\/jats:italic>\n                    and their possible associations with clinical phenotypes. In this work\n                    <jats:italic>LRBA<\/jats:italic>\n                    deficiency cases reported more than 11\u2009years ago have been revised. A database was constructed to analyze the type of variants, age at onset, clinical diagnosis, infections, autoimmune diseases, and cellular and immunoglobulin levels. The review of cases from 2012 to 2023 showed that\n                    <jats:italic>LRBA<\/jats:italic>\n                    deficiency was commonly diagnosed in patients with a clinical diagnosis of Common Variable Immunodeficiency, followed by enteropathy, neonatal diabetes mellitus, ALPS, and X\u2010linked\u2010like syndrome. Most cases show early onset of presentation at &lt;6\u2009years of age. Most cases lack protein expression, whereas hypogammaglobulinemia is observed in half of the cases, and IgG and IgA levels are isotypes reported at low levels. Patients with elevated IgG levels exhibited more than one autoimmune manifestation. Patients carrying pathogenic variants leading to a premature stop codon show a severe phenotype as they have an earlier onset of disease presentation, severe autoimmune manifestations, premature death, and low B cells and regulatory T cell levels. Missense variants were more common in patients with low IgG levels and cytopenia. This work lead to the conclusion that the type of variant in\n                    <jats:italic>LRBA<\/jats:italic>\n                    has association with disease severity, which leads to a premature stop codon being the ones that correlates with severe disease.\n                  <\/jats:p>","DOI":"10.1111\/pai.14179","type":"journal-article","created":{"date-parts":[[2024,6,23]],"date-time":"2024-06-23T02:09:12Z","timestamp":1719108552000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Analysis of\n                    <i>LRBA<\/i>\n                    pathogenic variants and the association with functional protein domains and clinical presentation"],"prefix":"10.1111","volume":"35","author":[{"given":"D.","family":"Perez\u2010Perez","sequence":"first","affiliation":[{"name":"Doctorate Program in Biological Sciences Autonomous National University of Mexico  Mexico City Mexico"},{"name":"Immunodeficiencies Laboratory National Institute of Pediatrics (INP)  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Santos\u2010Argumedo","sequence":"additional","affiliation":[{"name":"Biomedicine Department Center for Research and Advanced Studies of the National Polytechnic Institute (CINVESTAV)  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. C.","family":"Rodriguez\u2010Alba","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Neurooncology Unit The National Institute of Neurology and Neurosurgery (NINN)  Mexico City Mexico"},{"name":"Medicine and Surgery Faculty Autonomous University Benito Juarez from Oaxaca  Oaxaca Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5498-6739","authenticated-orcid":false,"given":"G.","family":"Lopez\u2010Herrera","sequence":"additional","affiliation":[{"name":"Immunodeficiencies Laboratory National Institute of Pediatrics (INP)  Mexico City Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.04.015"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.09.025"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-004-0027-2"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa1663"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2023.08.004"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.9.3947"},{"issue":"1","key":"e_1_2_11_8_1","first-page":"1004","article-title":"Lipopolysaccharide\u2010responsive beige\u2010like anchor (LRBA), a novel regulator of human immune disorders","volume":"1","author":"Wang J\u2010W","year":"2014","journal-title":"Aust J Clin 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