{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T18:14:17Z","timestamp":1755800057515,"version":"3.44.0"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"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:p>Familial hemophagocytic lymphohistiocytosis type 2 (FHL2), caused by perforin 1 (PRF 1), is a rare and fatal autosomal recessive disorder characterized by a hyperinflammatory syndrome and the accumulation of activated T lymphocytes and histiocytes in the reticuloendothelial system. Autoimmune lymphoproliferative syndrome (ALPS) is an autoimmune disease that typically presents in children with lymphadenopathy, splenomegaly, and cytopenias or lymphomas. We report a case of a 9-year-old boy who was newly diagnosed with FHL, carrying a new type of compound heterozygous mutations (c.305G&amp;gt;T and c.139G&amp;gt;T) in <jats:italic>PRF1<\/jats:italic> and a spontaneous heterozygous mutation in the <jats:italic>FAS<\/jats:italic> gene (c.776T&amp;gt;C). He met six of the eight hemophagocytic lymphohistiocytosis (HLH) diagnostic criteria: fever, splenomegaly, cytopenia, hypofibrinogenemia, hemophagocytosis in the bone marrow, and elevated sCD25. He also had a high proportion of CD3<jats:sup>+<\/jats:sup>CD4<jats:sup>\u2212<\/jats:sup>CD8<jats:sup>\u2212<\/jats:sup> T lymphocytes and a spontaneous mutation of <jats:italic>FAS<\/jats:italic>, which are features of ALPS. Chemotherapy failed to control the disease, and the child died within 3 months. <jats:italic>FAS<\/jats:italic> and <jats:italic>PRF1<\/jats:italic> comutation may have contributed to the adverse outcome in this patient. Notably, hematopoietic stem cell transplantation (HSCT) should be performed early in these patients.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1613433","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T05:34:40Z","timestamp":1755668080000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: FAS spontaneous mutation in a familial hemophagocytic lymphohistiocytosis patient with a complex heterozygous mutation in PRF1"],"prefix":"10.3389","volume":"16","author":[{"given":"Wenwen","family":"Ding","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danni","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa041432","article-title":"Inherited perforin and Fas mutations in a patient with autoimmune lymphoproliferative syndrome and 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