{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T13:51:12Z","timestamp":1781877072002,"version":"3.54.5"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:00:00Z","timestamp":1773532800000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin &amp;amp; Trans Imm"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      Inborn errors of immunity are rare genetic disorders that cause dysfunction of the immune system. Among these, familial haemophagocytic lymphohistiocytosis (FHL) involves defects in the perforin\/granzyme pathway, which is essential for regulating immune responses. These conditions predispose individuals to\u2009haemophagocytic lymphohistiocytosis, a life\u2010threatening hyperinflammatory syndrome. FHL has traditionally been described in paediatric patients with a fatal outcome in the absence of early haematopoietic stem cell transplantation. However, some patients harbouring missense mutations may present with atypical or late\u2010onset symptoms, for which management remains unstandardised.\u2009Among these reported variants, the pathogenicity of the A91V\u2009\n                      <jats:italic>PRF1<\/jats:italic>\n                      \u2009mutation remains the most controversial in the literature.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      We report\u2009clinical, biological and cytometric characteristics of\u2009two patients with a homozygous\u2009\n                      <jats:italic>PRF1<\/jats:italic>\n                      \u2009A91V mutation who developed clinical features consistent with FHL2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>We discuss the latest 2024 classifications to better characterise this group of disorders and their underlying genetic basis, with particular emphasis on atypical presentations and the A91V mutation, which may pose diagnostic and therapeutic challenges.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      A91V\u2009\n                      <jats:italic>PRF1<\/jats:italic>\n                      \u2009variant appears to represent a risk factor for the development of atypical FHL manifestations under divers triggers.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cti2.70081","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T03:21:09Z","timestamp":1773631269000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical, biological and cytometric characteristics of two patients with a homozygous\n                    <scp>A91V<\/scp>\n                    <i>PRF1<\/i>\n                    mutation"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1821-3464","authenticated-orcid":false,"given":"Nicolas","family":"Perrard","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Clinical Immunology CHU Lille  Lille France"},{"name":"Institute for Translational Research in Inflammation Univ. Lille, Inserm, CHU Lille, U1286 \u2010 INFINITE  Lille France"},{"name":"Regional Center for Primary Immune Deficiency CEREDIH, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Poggi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Immunology CHU Lille  Lille France"},{"name":"Regional Center for Primary Immune Deficiency CEREDIH, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Sanges","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Immunology CHU Lille  Lille France"},{"name":"Institute for Translational Research in Inflammation Univ. Lille, Inserm, CHU Lille, U1286 \u2010 INFINITE  Lille France"},{"name":"Regional Center for Primary Immune Deficiency CEREDIH, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Lemarchant","sequence":"additional","affiliation":[{"name":"Regional Center for Primary Immune Deficiency CEREDIH, CHU Lille  Lille France"},{"name":"Department of Neurology CRC\u2010SEP, CHU Lille  Lille France"},{"name":"LilNCog \u2010 Inserm U1172  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wadih Abou","family":"Chahlah","sequence":"additional","affiliation":[{"name":"Regional Center for Primary Immune Deficiency CEREDIH, CHU Lille  Lille France"},{"name":"Department of Paediatric Haematology CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Terriou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Immunology CHU Lille  Lille France"},{"name":"Institute for Translational Research in Inflammation Univ. Lille, Inserm, CHU Lille, U1286 \u2010 INFINITE  Lille France"},{"name":"Regional Center for Primary Immune Deficiency CEREDIH, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Delangue","sequence":"additional","affiliation":[{"name":"Regional Center for Primary Immune Deficiency CEREDIH, CHU Lille  Lille France"},{"name":"Paediatric Intensive Care Unit CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Trauet","sequence":"additional","affiliation":[{"name":"Institute for Translational Research in Inflammation Univ. Lille, Inserm, CHU Lille, U1286 \u2010 INFINITE  Lille France"},{"name":"Regional Center for Primary Immune Deficiency CEREDIH, CHU Lille  Lille France"},{"name":"Institute of Immunology CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Labalette","sequence":"additional","affiliation":[{"name":"Institute for Translational Research in Inflammation Univ. Lille, Inserm, CHU Lille, U1286 \u2010 INFINITE  Lille France"},{"name":"Regional Center for Primary Immune Deficiency CEREDIH, CHU Lille  Lille France"},{"name":"Institute of Immunology CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Hachulla","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Immunology CHU Lille  Lille France"},{"name":"Institute for Translational Research in Inflammation Univ. Lille, Inserm, CHU Lille, U1286 \u2010 INFINITE  Lille France"},{"name":"Regional Center for Primary Immune Deficiency CEREDIH, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despina","family":"Moshous","sequence":"additional","affiliation":[{"name":"Pediatric Immunology, Hematology and Rheumatology Necker\u2010Enfants Malades University Hospital, AP\u2010HP  Paris France"},{"name":"Laboratory of Genome Dynamics in the Immune System Imagine Institute, INSERM UMR  Paris France"},{"name":"Necker\u2010Enfants Malades University Hospital, AP\u2010HP, CEREDIH  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Lefevre","sequence":"additional","affiliation":[{"name":"Institute for Translational Research in Inflammation Univ. 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