{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:14:17Z","timestamp":1777652057808,"version":"3.51.4"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The study aims to report a rare case of a novel homozygous variant in the LRBA gene, originating from uniparental disomy of paternal origin. This case contributes new clinical data to the LRBA gene variant database.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study details the case of a 2-year-old child diagnosed in May 2023 at our center with a homozygous LRBA gene variant. Detailed clinical data of the patient were collected, including whole-exome sequencing of peripheral blood mononuclear cells, with parental genetic verification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The child presented with recurrent respiratory infections and chronic neutropenia, progressing to pancytopenia. Imaging showed splenomegaly and enlarged lymph nodes in the axillary and abdominal regions. Peripheral blood lymphocyte count revealed reduced B cells and NK cells. Elevated cytokine levels of IFN-\u03b1 and IFN-r were observed. Whole-exome sequencing revealed a nonsense homozygous variant in the LRBA gene, specifically c.2584C&amp;gt;T (p.Gln862Ter). The father exhibited a heterozygous variant at this locus, while no variant was found in the mother. Sample analysis indicated characteristics of uniparental disomy. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), this variant is preliminarily classified as \u201cLikely pathogenic\u201d. Currently, there are no reports in academic literature regarding this specific variant site.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>LRBA gene variants can lead to a rare inborn error of immunity disease. The c.2584C&amp;gt;T (p.Gln862Ter) variant in exon 22 of the LRBA gene is a newly identified pathogenic variant, and the homozygous variant caused by uniparental disomy is exceedingly rare. This case represents the second global report of an LRBA gene function loss due to uniparental disomy abnormalities.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1351076","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T04:21:06Z","timestamp":1709612466000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case report: A case of novel homozygous LRBA variant induced by chromosomal segmental uniparental disomy - genetic and clinical insights"],"prefix":"10.3389","volume":"15","author":[{"given":"Lihua","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-022-01352-z","article-title":"The 2022 update of IUIS phenotypical classification for human inborn errors of immunity","volume":"42","author":"Bousfiha","year":"2022","journal-title":"J\u00a0Clin Immunol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1016\/j.ajhg.2012.04.015","article-title":"Deleterious variants in LRBA are associated with a syndrome of immune deficiency and autoimmunity","volume":"90","author":"Lopez-Herrera","year":"2012","journal-title":"Am J Hum Genet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.jaci.2012.05.043","article-title":"LPS-responsive beige-like anchor LRBA gene variant in a family with inflammatory bowel disease and combined immunodeficiency [J]","volume":"130","author":"Alangari","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s10875-015-0224-7","article-title":"Spectrum of phenotypes associated with variants in LRBA","volume":"36","author":"Alkhairy","year":"2016","journal-title":"J Clin Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.09.025","article-title":"The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency","volume":"137","author":"G\u00e1mez-D\u00edaz","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa1663","article-title":"Autoimmune Disease. 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