{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T03:27:17Z","timestamp":1794454037830,"version":"4.9.1"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004462","name":"Consiglio Nazionale delle Ricerche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004462","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2026,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Introduction<\/jats:title>\n \n Haemophilia B (HB) associates with deleterious variants in\n F9<\/jats:italic>\n . HB management with FIX\u2010concentrate infusions may be ineffective in 3%\u20139% patients who develop FIX\u2010inhibitors.\n <\/jats:p>\n <\/jats:sec>\n \n Aim<\/jats:title>\n \n To present our HB\u2010series (\n n<\/jats:italic>\n = 136) including all Argentinean patients with FIX\u2010inhibitors (\n n<\/jats:italic>\n = 13). To estimate\n F9<\/jats:italic>\n \u2010genotype\u2010associated FIX\u2010inhibitor risks from our series (GMH), and HB\u2010international databases, FIX\u2010UCL and EAHAD.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n F9<\/jats:italic>\n \u2010genotyping was performed by conventional protocols; or by short\u2010read\u2010NGS on a new\n F9<\/jats:italic>\n \u2010panel. FIX\u2010inhibitor risks were estimated by case(inh+)\/control(inh\u2010) studies using OR(95%CI).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The spectrum of\n F9<\/jats:italic>\n \u2010genotypes from our GMH\u2010series resulted similar to the one compiled in international databases, prevailing missense (45%), and nonsense (21%) in severe\u2010HB and missense defects (> 80%) in non\u2010severe\u2010HB. Our set of HB\u2010patients with FIX\u2010inhibitors mostly included large\u2010deletions and nonsense mutations, and 38.5% developed allergic reactions. Case\/Control studies mainly aligned FIX\u2010inhibitor risks in all three datasets. Considering severe\u2010HB in GMH(\n n<\/jats:italic>\n = 91)\/\/FIX\u2010UCL(\n n<\/jats:italic>\n = 349)\/\/EAHAD(\n n<\/jats:italic>\n = 590), we observed a high\u2010risk group that comprised entire\u2010\n F9<\/jats:italic>\n \u2010deletions with highly\u2010significant ORs of 24\/\/12\/\/35, all\u2010large\u2010deletions, 7\/\/7\/\/17 and nonsense mutations, 3\/\/3\/\/2; and a low\u2010risk group confined to missense\n F9<\/jats:italic>\n \u2010variants with highly\u2010significant protective ORs, 0.04\/\/0.11\/\/0.03, whilst other\n F9<\/jats:italic>\n \u2010variants did not differ from the null\u2010hypothesis. Equal analysis from all\u2010severities HB patients closely agreed with these results. An analysis of NS and FIX\u2010inhibitor risks suggested the involvement of nonsense\u2010mediated decay (NMD) in\n F9<\/jats:italic>\n : nonsense (\n F9<\/jats:italic>\n \u2010exons_1\u20137)\n vs<\/jats:italic>\n nonsense (\n F9<\/jats:italic>\n \u2010exon_8) resulted in highly\u2010significantly incremented risks in both FIX\u2010UCL(\n n<\/jats:italic>\n = 124)\/\/EAHAD(\n n<\/jats:italic>\n = 171), ORs of 4(2\u20139)\/\/4(3\u20136).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Our study provides robust estimations of\n F9<\/jats:italic>\n \u2010genotype\u2010associated FIX\u2010inhibitor risks in HB\u2010patients and exposed the involvement of NMD.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/hae.70356","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:01:23Z","timestamp":1784541683000},"page":"1488-1497","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Analysis of the FIX\u2010inhibitor Risks Associated With the\n F9<\/i>\n Genotype in Patients With Haemophilia B Exposes the Involvement of Nonsense Mediated\u2010Decay: Argentinean and International Series"],"prefix":"10.1111","volume":"32","author":[{"given":"Betiana Michelle","family":"Ziegler","sequence":"first","affiliation":[{"name":"Instituto De Medicina Experimental (IMEX) (CONICET\u2010Academia Nacional de Medicina) Ciudad de Buenos Aires Argentina"},{"name":"Instituto De Investigaciones Hematol\u00f3gicas Mariano Castex (IIHEMA) (Academia Nacional de Medicina) Ciudad de Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel Mart\u00edn","family":"Abelleyro","sequence":"additional","affiliation":[{"name":"Instituto De Medicina Experimental (IMEX) (CONICET\u2010Academia Nacional de Medicina) Ciudad de Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Emilia","family":"Villegas","sequence":"additional","affiliation":[{"name":"Unidad Operativa Centro Nacional de Gen\u00f3mica y Bioinform\u00e1tica (UOCNGyB) Administraci\u00f3n Nacional de Laboratorios e Institutos De Salud (ANLIS) \u201cDr. Carlos G. Malbr\u00e1n\u201d Ciudad de Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juli\u00e1n Sanchez","family":"Loria","sequence":"additional","affiliation":[{"name":"Unidad Operativa Centro Nacional de Gen\u00f3mica y Bioinform\u00e1tica (UOCNGyB) Administraci\u00f3n Nacional de Laboratorios e Institutos De Salud (ANLIS) \u201cDr. Carlos G. Malbr\u00e1n\u201d Ciudad de Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9ctor Mart\u00edn","family":"Cifuentes","sequence":"additional","affiliation":[{"name":"Instituto De Medicina Experimental (IMEX) (CONICET\u2010Academia Nacional de Medicina) Ciudad de Buenos Aires Argentina"},{"name":"Unidad De Conocimiento Traslacional Hospitalaria Patag\u00f3nica (UCTHP) Hospital de Alta Complejidad El Calafate SAMIC, Santa Cruz El Calafate Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Neme","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n de la Hemofilia Alfredo Pavlovsky Ciudad de Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Sciuccati","sequence":"additional","affiliation":[{"name":"Hospital De Pediatr\u00eda S.A.M.I.C. \u201cProf. Dr. Juan P. 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