{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T11:17:20Z","timestamp":1771931840469,"version":"3.50.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      X-linked MAGT1 deficiency with increased susceptibility to EBV-infection and N-linked glycosylation (XMEN) disease is an inborn error of immunity (IEI) affecting the Magnesium Transporter 1 (\n                      <jats:italic>MAGT1)<\/jats:italic>\n                      gene. In this report, we present the diagnostic odyssey for a patient harboring a novel\n                      <jats:italic>MAGT1<\/jats:italic>\n                      variant resulting in XMEN disease.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      A 6y old male child of Caucasian ancestry presented at the immunology clinic in our hospital with a history of recurrent upper respiratory tract infections, as well as significant atopy and viral skin lesions. Genetic testing identified a novel, hemizygous pathogenic variant in the magnesium transporter 1 (\n                      <jats:italic>MAGT1<\/jats:italic>\n                      ) gene (c.580dup; p.Ser194Phefs*3). Follow-up testing by flow cytometry revealed the canonical disruption in Natural Killer Group 2D (NKG2D) surface expression on CD8 T cells and NK cells, and clinical testing for congenital disorders of glycosylation (CDG) additionally verified the hallmark defect in glycosylation that underpins XMEN disease. Subsequent\n                      <jats:italic>in silico<\/jats:italic>\n                      analyses using AlphaFold provided an in-depth view of the resulting aberrant protein structural variant and its inability to tether itself to the OST-B complex, a pre-requisite for optimal enzymatic activity of the MAGT1 protein. Disease management included infection control and prophylaxis, steroids and immunotherapy for the patient\u2019s asthma and atopy, topical antiviral treatment for the warts and molluscum, as well as biannual EBV load monitoring (the patient is EBV negative).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This case illustrates how a synergistic multi-disciplinary team approach established a diagnosis of XMEN disease in a patient with an atypical clinical presentation. This case also highlights a growing trend where established diagnostic tools such as flow-cytometry and genomics can be complemented with newer, sophisticated analytical approaches such as AlphaFold to further elucidate the functionally crippling effects of novel variants described in the setting of IEI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1754394","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T05:19:09Z","timestamp":1771219149000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Novel MAGT1 pathogenic variant with significant atopy, hypogammaglobulinemia and viral skin infections"],"prefix":"10.3389","volume":"17","author":[{"given":"Lauren","family":"Gunderman","sequence":"first","affiliation":[{"name":"Division of Allergy and Immunology, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago","place":["Chicago, IL, United States"]},{"name":"Department of Pediatrics, Northwestern University Feinberg School of Medicine","place":["Chicago, IL, United States"]},{"name":"Department of Pediatrics, University of Washington School of Medicine","place":["Seattle, WA, United States"]},{"name":"Division of Immunology, Seattle Children\u2019s Hospital","place":["Seattle, WA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher P.","family":"Ptak","sequence":"additional","affiliation":[{"name":"Biomolecular Nuclear Magnetic Resonance Facility, University of Iowa","place":["Iowa City, IA, United States"]},{"name":"Department of Molecular Physiology and Biophysics, Carver College of Medicine, University of Iowa","place":["Iowa City, IA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madeline","family":"Schutt","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago","place":["Chicago, IL, United States"]},{"name":"Department of Pediatrics, Northwestern University Feinberg School of Medicine","place":["Chicago, IL, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kento","family":"Yahashiri","sequence":"additional","affiliation":[{"name":"Biological Sciences, Northwestern University","place":["Evanston, IL, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Lippner","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago","place":["Chicago, IL, United States"]},{"name":"Department of Pediatrics, Northwestern University Feinberg School of Medicine","place":["Chicago, IL, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amer","family":"Khojah","sequence":"additional","affiliation":[{"name":"College of Medicine, Umm Al-Qura University","place":["Makkah, Saudi Arabia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aisha","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago","place":["Chicago, IL, United States"]},{"name":"Department of Pediatrics, Northwestern University Feinberg School of Medicine","place":["Chicago, IL, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaruni","family":"Khanolkar","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Iowa, Carver College of Medicine, University of Iowa","place":["Iowa City, IA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10246","article-title":"Second messenger role for Mg2+ revealed by human T-cell immunodeficiency","volume":"475","author":"Li","year":"2011","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1684\/mrh.2011.0286","article-title":"Loss of MAGT1 abrogates the Mg2+ flux required for T cell 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