{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:00:47Z","timestamp":1775804447994,"version":"3.50.1"},"reference-count":11,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"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. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To characterize the immune and molecular abnormalities underlying MIRAGE syndrome by profiling peripheral blood transcriptomes and assessing immune cell composition and function in affected patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed RNA sequencing on peripheral whole-blood samples collected from identical twins diagnosed with MIRAGE syndrome and their healthy parents. Bulk RNA-seq data were subsequently deconvoluted to assess the composition, state, and functional characteristics of immune cell populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Differentially expressed genes between patients and healthy parents were significantly enriched in the PI3K\u2013Akt signaling pathway, B-cell receptor signaling pathway, and primary immunodeficiency-related pathways. Patients exhibited reduced proportions of memory and na\u00efve B cells, accompanied by increased proportions of CD8\u2005T cells and M2 macrophages. We further identified the top 10 hub genes, which showed moderate to strong correlations with B-cell differentiation, proliferation, and activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Immune cell dysregulation is evident in patients with MIRAGE syndrome, with B-cell abnormalities representing a prominent immunological feature.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1765896","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:05:28Z","timestamp":1775801128000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Hidden B-cell dysregulation in MIRAGE syndrome"],"prefix":"10.3389","volume":"14","author":[{"given":"Shulan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Children\u2019s Hospital of Nanjing Medical University , , .","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Children\u2019s Hospital of Nanjing Medical University , , .","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Children\u2019s Hospital of Nanjing Medical University , , .","place":["Nanjing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1038\/ng.3569","article-title":"SAMD9 Mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7","volume":"48","author":"Narumi","year":"2016","journal-title":"Nat Genet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1172\/jci91913","article-title":"Somatic mutations and progressive monosomy modify SAMD9-related phenotypes in humans","volume":"127","author":"Buonocore","year":"2017","journal-title":"J Clin Invest"},{"key":"B3","doi-asserted-by":"publisher","first-page":"953707","DOI":"10.3389\/fendo.2022.953707","article-title":"Emerging phenotypes linked to variants in SAMD9 and MIRAGE syndrome","volume":"13","author":"Suntharalingham","year":"2022","journal-title":"Front Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1297\/cpe.28.147","article-title":"MIRAGE Syndrome with recurrent pneumonia probably associated with gastroesophageal reflux and achalasia: a case report","volume":"28","author":"Yoshizaki","year":"2019","journal-title":"Clin Pediatr Endocrinol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s10875-024-01808-4","article-title":"Novel SAMD9 variant causing MIRAGE syndrome treated with subcutaneous immunoglobulin","volume":"45","author":"Peek","year":"2024","journal-title":"J Clin Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2194","DOI":"10.3389\/fimmu.2019.02194","article-title":"Novel SAMD9 mutation in a patient with immunodeficiency, neutropenia, impaired anti-CMV response, and severe gastrointestinal involvement","volume":"10","author":"Formankova","year":"2019","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1111\/crj.13702","article-title":"Deconvolution of bulk RNA sequencing in activated phosphoinositide 3-kinase \u03b4 syndrome","volume":"17","author":"Huang","year":"2023","journal-title":"Clin Respir J"},{"key":"B8","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"Edger: a bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"B9","doi-asserted-by":"publisher","first-page":"188952","DOI":"10.1016\/j.bbcan.2023.188952","article-title":"PI3K signaling-regulated metabolic reprogramming: from mechanism to application","volume":"1878","author":"Su","year":"2023","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"B10","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/s12264-019-00436-y","article-title":"Homeobox B8 targets Sterile alpha motif domain-containing protein 9 and drives glioma progression","volume":"36","author":"Ma","year":"2020","journal-title":"Neurosci Bull"},{"key":"B11","doi-asserted-by":"publisher","first-page":"659659","DOI":"10.3389\/fimmu.2021.659659","article-title":"SAMD9 Is relating with M2 macrophage and remarkable malignancy characters in low-grade glioma","volume":"12","author":"Ma","year":"2021","journal-title":"Front Immunol"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1765896\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:05:38Z","timestamp":1775801138000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1765896\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,10]]},"references-count":11,"alternative-id":["10.3389\/fped.2026.1765896"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1765896","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,10]]},"article-number":"1765896"}}