{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T13:21:13Z","timestamp":1762089673135,"version":"build-2065373602"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["pericles.pericles-gcp.literatumonline.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Dominant\u2010negative effects have been described for 10\u00a0<jats:italic>F11<\/jats:italic> variants in the literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>The current study aimed at identifying putative dominant\u2010negative <jats:italic>F11<\/jats:italic> variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>This research consisted in a retrospective analysis of routine laboratory data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In a series of 170\u00a0patients with moderate\/mild factor\u00a0XI (FXI) deficiencies, we identified heterozygous carriers of previously reported dominant\u2010negative variants (p.Ser243Phe, p.Cys416Tyr, and p.Gly418Val) with FXI activities inconsistent with a dominant\u2010negative effect. Our findings also do not support a dominant\u2010negative effect of p.Gly418Ala. We also identified a set of patients carrying heterozygous variants, among which five out of 11 are novel, with FXI activities suggesting a dominant\u2010negative effect (p.His53Tyr, p.Cys110Gly, p.Cys140Tyr, p.Glu245Lys, p.Trp246Cys, p.Glu315Lys, p.Ile421Thr, p.Trp425Cys, p.Glu565Lys, p.Thr593Met, and p.Trp617Ter). However, for all but two of these variants, individuals with close to half normal FXI coagulant activity (FXI:C) were identified, indicating an inconstant dominant effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data show that for some <jats:italic>F11<\/jats:italic> variants recognized has having dominant\u2010negative effects, such effects actually do not occur in many individuals. The present data suggest that for these patients, the intracellular quality control mechanisms eliminate the variant monomeric polypeptide before homodimer assembly, thereby allowing only the wild\u2010type homodimer to assemble and resulting in half normal activities. In contrast, in patients with markedly decreased activities, some mutant polypeptides might escape this first quality control. In turn, assembly of heterodimeric molecules as well as mutant homodimers would result in activities closer to 1:4 of FXI:C normal range.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14802","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T17:09:45Z","timestamp":1685466585000},"page":"1113-1120","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A focus on dominant negative variants in a series of 170 heterozygous FXI\u2010deficient patients"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8091-9882","authenticated-orcid":false,"given":"Philippe","family":"de Mazancourt","sequence":"first","affiliation":[{"name":"UMR1179 Universit\u00e9 de Versailles\u2010Saint\u2010Quentin  Montigny le Bretonneux France"},{"name":"Laboratoire de Biologie Mol\u00e9culaire H\u00f4pital A. Par\u00e9 APHP.Paris\u2010Saclay  Boulogne\u2010Billancourt France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Florence","family":"Qu\u00e9lin","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Recherche Clinique CH Versailles  Le Chesnay France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Flaujac","sequence":"additional","affiliation":[{"name":"Laboratoire de biologie m\u00e9dicale secteur h\u00e9mostase centre hospitalier de Versailles (Andr\u00e9 Mignot)  Le Chesnay France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8774-3162","authenticated-orcid":false,"given":"Emmanuelle","family":"de Raucourt","sequence":"additional","affiliation":[{"name":"Centre de Ressources et de Comp\u00e9tences Maladies H\u00e9morragiques Constitutionnelles CH de Versailles  Le Chesnay France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2938-8013","authenticated-orcid":false,"given":"Beno\u00eet","family":"Guillet","sequence":"additional","affiliation":[{"name":"Centre de Traitement des maladies h\u00e9morragiques Univ Rennes CHU Rennes Inserm EHESP Irset (Institut de recherche en sant\u00e9, environnement et travail) \u2010 UMR_S 1085  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Bauduer","sequence":"additional","affiliation":[{"name":"Service d'H\u00e9matologie Centre Hospitalier de la C\u00f4te Basque Bayonne, and UMR 5199 PACEA Universit\u00e9 de Bordeaux  Pessac France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Ernest","sequence":"additional","affiliation":[{"name":"Laboratoire d'H\u00e9matologie CHU la Timone  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Beurrier","sequence":"additional","affiliation":[{"name":"Laboratoire d'H\u00e9matologie CHU d'Angers  Angers France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aur\u00e9lie","family":"Avril","sequence":"additional","affiliation":[{"name":"UMR1179 Universit\u00e9 de Versailles\u2010Saint\u2010Quentin  Montigny le Bretonneux France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4843-7805","authenticated-orcid":false,"given":"Roseline","family":"d'Oiron","sequence":"additional","affiliation":[{"name":"Centre de Traitement de l'H\u00e9mophilie \u2010 CRTH \u2010 CHU Paris\u2010Sud \u2010 H\u00f4pital de Bic\u00eatre APHP.Paris\u2010Saclay  Le Kremlin\u2010Bic\u00eatre France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7549-8718","authenticated-orcid":false,"given":"Christine","family":"Biron\u2010Andr\u00e9ani","sequence":"additional","affiliation":[{"name":"Centre de Traitement de l'H\u00e9mophilie (CTH) Centre de Ressources et de Comp\u00e9tences Maladies H\u00e9morragiques Constitutionnelles (CRC\u2010MHC) \u2013 H\u00f4pital St\u2010Eloi CHU Montpellier  Montpellier France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandrine","family":"Meunier","sequence":"additional","affiliation":[{"name":"Hospices civils de Lyon; 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