{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T22:41:43Z","timestamp":1772232103674,"version":"3.50.1"},"reference-count":19,"publisher":"American Academy of Pediatrics (AAP)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,10,1]]},"abstract":"<jats:p>This article presents a case report for a child presenting with mixed clinical features of autoimmune lymphoproliferative syndrome (ALPS), familial hemophagocytic lymphohistiocytosis (FHL), and X-linked lymphoproliferative (XLP) disease. From 6 months, he exhibited splenomegaly and lymphoadenopathy and from 4 years, he showed recurrent severe autoimmune hemocytopenia and sepsislike bouts of fever, from which he eventually died at the age of 12. Intriguingly, the patient carried mutations in FAS, XIAP, and UNC13D genes, which are involved in ALPS, XLP disease, and FHL, respectively. These mutations were inherited from the mother, who had rheumatoid arthritis but no signs of ALPS. A role for other modifying genes was suggested by the finding that the healthy father exhibited defective Fas function, without mutation of the FAS gene, and had transmitted to the patient an osteopontin (OPN) gene variant previously associated with ALPS. Therefore, several genes might influence the disease outcome in this family. In vitro analyses revealed that the FAS and the XIAP mutations decreased expression of the corresponding proteins, and the UNC13D mutation decreased granule secretion and Munc interaction with Rab-27a. These findings suggest that overlap may exist between ALPS, FHL, and XLP disease, in accordance with the notion that FHL and XLP disease are due to defective natural killer (NK)\/NK T\u2013cell function, which involves Fas. Therefore, we propose that NK cell defects should be evaluated in patients with ALPS-like characteristics, and hematopoietic stem cell transplantation should be considered in individuals with severe refractory cytopenia and FHL-like manifestations.<\/jats:p>","DOI":"10.1542\/peds.2012-1838","type":"journal-article","created":{"date-parts":[[2013,9,16]],"date-time":"2013-09-16T21:09:50Z","timestamp":1379365790000},"page":"e1052-e1058","source":"Crossref","is-referenced-by-count":18,"title":["Mutation of\n                    <i>FAS<\/i>\n                    ,\n                    <i>XIAP<\/i>\n                    , and\n                    <i>UNC13D<\/i>\n                    Genes in a Patient With a Complex Lymphoproliferative Phenotype"],"prefix":"10.1542","volume":"132","author":[{"given":"Elena","family":"Boggio","sequence":"first","affiliation":[{"name":"Interdisciplinary Research Center of Autoimmune Diseases and Department of Health Sciences, \u201cA. Avogadro\u201d University of Eastern Piedmont, Novara, Italy;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Aric\u00f2","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology Oncology, Azienda-Ospedaliero Universitaria Meyer Children\u2019s Hospital, Florence, Italy; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matteo","family":"Melensi","sequence":"additional","affiliation":[{"name":"Interdisciplinary Research Center of Autoimmune Diseases and Department of Health Sciences, \u201cA. Avogadro\u201d University of Eastern Piedmont, Novara, Italy;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irma","family":"Dianzani","sequence":"additional","affiliation":[{"name":"Interdisciplinary Research Center of Autoimmune Diseases and Department of Health Sciences, \u201cA. Avogadro\u201d University of Eastern Piedmont, Novara, Italy;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ugo","family":"Ramenghi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Torino, Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Umberto","family":"Dianzani","sequence":"additional","affiliation":[{"name":"Interdisciplinary Research Center of Autoimmune Diseases and Department of Health Sciences, \u201cA. Avogadro\u201d University of Eastern Piedmont, Novara, Italy;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annalisa","family":"Chiocchetti","sequence":"additional","affiliation":[{"name":"Interdisciplinary Research Center of Autoimmune Diseases and Department of Health Sciences, \u201cA. 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