{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:11:11Z","timestamp":1747185071670,"version":"3.40.5"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T00:00:00Z","timestamp":1664841600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Data on failure to identify the molecular mechanism underlying FXI deficiency by Sanger analysis and the contribution of gene segment deletions are almost inexistent.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims and methods<\/jats:title><jats:p>Prospective and retrospective analysis was conducted on FXI\u2010deficient patients\u2019 DNA via Next Generation Sequencing (NGS), or Sanger sequencing and Multiplex Probe Ligation\u2010dependent Assay (MLPA) to detect cryptic causative gene variants or gene segment deletions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sanger analysis or NGS enabled us to identify six severe and one partial (median activity 41\u00a0IU\/dl) FXI deficient index cases with deletions encompassing exons 11\u201315, the whole gene, or both. After Sanger sequencing, retrospective evaluation using MLPA detected seven additional deletion cases in apparently homozygous cases in non\u2010consanguineous families, or in previously unsolved FXI\u2010deficiency cases. Among the 504 index cases with a complete genetic investigation (Sanger\/MLPA, or NGS), 23 remained unsolved (no abnormality found [<jats:italic>n<\/jats:italic>\u00a0=\u00a014] or rare intronic variants currently under investigation, [<jats:italic>n<\/jats:italic>\u00a0=\u00a09]). In the 481 solved cases (95% efficiency), we identified <jats:italic>F11<\/jats:italic> gene\u2010deleted patients (14 cases; 2.9%). Among these, whole gene deletion accounted for four heterozygous cases, exons 11\u201315 deletion for five heterozygous and three homozygous ones, while compound heterozygous deletion and isolated exon 12 deletion accounted for one case each.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Given the high incidence of deletions in our population (2.9%), MLPA (or NGS with a reliable bioinformatic pipeline) should be systematically performed for unsolved FXI deficiencies or apparently homozygous cases in non\u2010consanguineous families.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14666","type":"journal-article","created":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T22:49:37Z","timestamp":1664923777000},"page":"248-255","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reinvestigation of unidentified causative variants in FXI\u2010deficient patients: Focus on gene segment deletions"],"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":"Laboratory of Molecular Biology Ambroise Pare Hospital, GHU APHP Paris\u2010Saclay  Boulogne\u2010Billancourt France"},{"name":"UMR1179 Versailles St\u2010Quentin University  Boulogne\u2010Billancourt France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7368-4624","authenticated-orcid":false,"given":"Annie","family":"Harroche","sequence":"additional","affiliation":[{"name":"Department of Hematology Hospital Necker\u2010Enfants Malades, GHU AP\u2010HP, Centre \u2010 Universit\u00e9 de Paris  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katia","family":"Pouymayou","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology La Timone Hospital, APHM  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Sigaud","sequence":"additional","affiliation":[{"name":"Ressources and Competence Center for Constitutional Bleeding Disorders \u2010 CRC\u2010MHC Nantes University Hospital  Nantes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9line","family":"Falaise","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Immunology, and Oncology La Timone Children's Hospital, APHM  Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Stieltjes","sequence":"additional","affiliation":[{"name":"Ressources and Competence Center for Constitutional Bleeding Disorders \u2010 CRC\u2010MHC Cochin Hospital, GHU AP\u2010HP, Centre \u2010 Universit\u00e9 de Paris  Paris 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