{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T21:45:15Z","timestamp":1768254315244,"version":"3.49.0"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"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. Genet."],"abstract":"\n Objective<\/jats:title>\n \n The study aims to describe the clinical manifestations, immunophenotype, and gene mutation characteristics of a child with X-linked severe combined immunodeficiency (X-SCID) caused by an\n IL2RG<\/jats:italic>\n mutation (NM_000206.3; exon 2 c.216C &gt; A, p.Cys72*), and to contextualize these findings through a review of reported cases of X-SCID associated with\n Talaromyces marneffei<\/jats:italic>\n (\n T. marneffei<\/jats:italic>\n ) infection, highlighting the immunological and diagnostic relevance of the mutation.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The clinical data of a child with X-SCID caused by an\n IL2RG<\/jats:italic>\n mutation were retrospectively analyzed. Whole-exome sequencing and Sanger sequencing were used to identify the mutation, and flow cytometry was employed for immunophenotypic analysis to assess the impact of the mutation on immune function. A literature review was performed on reported cases of X-SCID associated with\n T. marneffei<\/jats:italic>\n infection identified in PubMed and Scopus.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The patient was a 4-month-old male infant presenting with chronic diarrhea, recurrent fever, and anemia, with poor response to antibiotic treatment. Laboratory tests indicated\n T. marneffei<\/jats:italic>\n infection, significantly reduced T lymphocytes and NK cells, and decreased levels of immunoglobulins (IgG, IgA, IgE). Genetic testing revealed a\n de novo<\/jats:italic>\n hemizygous mutation in the\n IL2RG<\/jats:italic>\n gene (NM_000206.3; exon2 c.216C &gt; A, p.Cys72*), which has not been previously reported. Flow cytometric analysis showed a severe reduction in T lymphocytes, absence of CD8\n +<\/jats:sup>\n T cells, reduced NK cells, and a normal number of B lymphocytes. Six cases of\n IL2RG<\/jats:italic>\n gene mutation combined with\n T. marneffei<\/jats:italic>\n infection were identified in the literature, most showing fever, hepatosplenomegaly and respiratory tract infection.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n This case of X-SCID caused by a novel\n de novo IL2RG<\/jats:italic>\n mutation expands the known mutation spectrum and highlights its immunological and diagnostic relevance. The review of reported cases of X-SCID with\n T. marneffei<\/jats:italic>\n infection further clarifies genotype\u2013phenotype correlations and supports improved recognition of such rare presentations.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fgene.2025.1641956","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T05:35:09Z","timestamp":1759815309000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A novel de novo IL2RG nonsense mutation in a pediatric patient with X-linked severe combined immunodeficiency"],"prefix":"10.3389","volume":"16","author":[{"given":"Lin","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiyan","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sixi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuochen","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"B31","doi-asserted-by":"publisher","first-page":"623199","DOI":"10.3389\/fimmu.2020.623199","article-title":"A Decade Experience on Severe Combined Immunodeficiency Phenotype in Oman, Bridging to Newborn Screening","volume":"11","author":"Al Sukaiti","year":"2021","journal-title":"Front. 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