{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T06:12:30Z","timestamp":1776147150716,"version":"3.50.1"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"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>Introduction<\/jats:title>\n                    <jats:p>\n                      Severe combined immunodeficiency (SCID) comprises a group of life-threatening inborn errors of immunity (IEI) characterized by profound T-cell deficiency, frequently accompanied by impaired B cell and natural killer (NK) cell function. X-linked SCID (X-SCID), caused by pathogenic variants in\n                      <jats:italic>IL2RG<\/jats:italic>\n                      , accounts for approximately 30% of all SCID cases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We describe two male siblings born to consanguineous parents with a family history of early sibling deaths due to severe infections. Patient 1 was a 9-month-old boy who developed persistent cough, chronic diarrhea, and subcutaneous nodules following Bacillus\n                      <jats:italic>Calmette\u2013Gu\u00e9rin<\/jats:italic>\n                      (BCG) vaccination. He was subsequently diagnosed with disseminated BCG infection with concomitant\n                      <jats:italic>Salmonella<\/jats:italic>\n                      co-infection. Immunological evaluation revealed a T\u2212B+NK\u2212 phenotype. Despite intensive antimicrobial treatment, he died of septic shock at 12 months of age. Patient 2, a one-month-old boy, was evaluated early in life because of family history. Immunophenotyping demonstrated absent T cells, normal B cells, and reduced NK cells, along with the absence of a thymic shadow on chest radiography. Next-generation sequencing identified a hemizygous\n                      <jats:italic>IL2RG<\/jats:italic>\n                      c.667G&amp;gt;T (p.V223F). He received antimicrobial prophylaxis and immunoglobulin replacement therapy; however, he developed disseminated adenovirus infection and died at 8 months of age. Molecular Findings:\n                      <jats:italic>In silico<\/jats:italic>\n                      analyses (UniProt, HOPE, dbNSFP) consistently supported the pathogenic effect of the variant\n                      <jats:italic>IL2RG<\/jats:italic>\n                      p.V223F. Based on this evidence, we propose that its current classification as \u201clikely pathogenic\u201d should be updated to \u201cpathogenic\u201d.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These cases underscore the challenges faced by patients with SCID when timely access to curative therapy is not available. They also highlight the importance of readily accessible but highly informative diagnostic clues, such as the absence of a thymic shadow on chest radiography and the occurrence of severe complications following BCG vaccination. Conclusions: This report expands the known genotypic and phenotypic spectrum of SCID and reinforces the critical need for early diagnosis, appropriate genetic counseling in consanguineous families, and equitable access to newborn screening programs and curative treatments, including hematopoietic stem cell transplantation and gene therapy, in order to improve survival outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1776191","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T05:36:55Z","timestamp":1776145015000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["X-linked severe combined immunodeficiency due to IL2RG p.V223F variant: clinical evidence that support its pathogenicity- a case report"],"prefix":"10.3389","volume":"17","author":[{"given":"Bricia Melissa","family":"Guti\u00e9rrez-Zepeda","sequence":"first","affiliation":[{"name":"Doctorado en Gen\u00e9tica Humana, Departamento de Biolog\u00eda Molecular y Gen\u00f3mica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara","place":["Guadalajara, Mexico"]},{"name":"Instituto de Investigaci\u00f3n en Inmunolog\u00eda, Departamento de Fisiolog\u00eda, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara","place":["Guadalajara, Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan Carlos","family":"Lona-Reyes","sequence":"additional","affiliation":[{"name":"Departamento de Infectolog\u00eda, Nuevo Hospital Civil de Guadalajara \u201cDr. Juan I. Menchaca\u201d","place":["Guadalajara, Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario Ernesto","family":"Cruz-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad Aut\u00f3noma del Estado de Morelos","place":["Cuernavaca, Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Quintero-Ramos","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Inmunolog\u00eda, Departamento de Fisiolog\u00eda, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara","place":["Guadalajara, Mexico"]},{"name":"Unidad de Investigaci\u00f3n Biom\u00e9dica 02, Unidad M\u00e9dica de Alta Especialidad (UMAE), Hospital de Especialidades, Centro M\u00e9dico Nacional de Occidente, Instituto Mexicano de Seguro Social (IMSS)","place":["Guadalajara, Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Torres-Lozano","sequence":"additional","affiliation":[{"name":"Ex Jefe del departamento de Inmunolog\u00eda Cl\u00ednica y Alergia, Hospital de Especialidades, Centro M\u00e9dico Nacional de Occidente, Instituto Mexicano de Seguro Social (IMSS)","place":["Guadalajara, Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Bayardo-Gutierrez","sequence":"additional","affiliation":[{"name":"Departamento de Alergia e Inmunolog\u00eda Cl\u00ednica Pedi\u00e1trica, Nuevo Hospital Civil de Guadalajara \u201cDr. Juan I. Menchaca\u201d","place":["Guadalajara, Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro","family":"Barr\u00f3n-Balderas","sequence":"additional","affiliation":[{"name":"Departamento de Cl\u00ednicas de la Reproducci\u00f3n Humana, Crecimiento y Desarrollo Infantil, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara","place":["Guadalajara, Mexico"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio D.","family":"Rosenzweig","sequence":"additional","affiliation":[{"name":"Immunology Service, Department of Laboratory Medicine, National Institutes of Health (NIH) Clinical Center, NIH","place":["Bethesda, MD, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Stoddard","sequence":"additional","affiliation":[{"name":"Immunology Service, Department of Laboratory Medicine, National Institutes of Health (NIH) Clinical Center, NIH","place":["Bethesda, MD, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Niemela","sequence":"additional","affiliation":[{"name":"Immunology Service, Department of Laboratory Medicine, National Institutes of Health (NIH) Clinical Center, NIH","place":["Bethesda, MD, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Enriqueta","family":"N\u00fa\u00f1ez-N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Departamento de Alergia e Inmunolog\u00eda Cl\u00ednica Pedi\u00e1trica, Nuevo Hospital Civil de Guadalajara \u201cDr. Juan I. 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