{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T07:53:46Z","timestamp":1773388426290,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T00:00:00Z","timestamp":1697414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Factor X deficiency is a rare inherited bleeding disorder. To date, 181 variants are reported in the recently updated <jats:italic>F10<\/jats:italic>\u2010gene variant database.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>This study aimed to describe new <jats:italic>F10<\/jats:italic> variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>The <jats:italic>F10<\/jats:italic> gene was analysed in 16 consecutive families with FX deficiency by a targeted high\u2010throughput sequencing approach, including <jats:italic>F10<\/jats:italic>, <jats:italic>F9, F8<\/jats:italic> genes, and 78 genes dedicated to haematological malignancies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 19 variants (17 missense, one nonsense and one frameshift) and two copy number variations. Two patients presenting a combined FVII\u2010FX deficiency showed a loss of one <jats:italic>F10<\/jats:italic> gene copy (del13q34) associated with a missense variant on the remaining allele, leading to a FX:C significantly lower than the FVII:C level and explaining their unusual bleeding history. We reported five novel variants. Three missense variants (p.Glu22Val affecting the signal peptide cleavage site, p.Cys342Tyr removing the disulphide bond between the FX heavy and light chains, and p.Val385Met located in FX peptidase S1 domain) were detected at compound heterozygosis status in three patients with severe bleeding symptoms and FX:C level below 10 IU\/dL. Two truncating variants p.Tyr279* and p.Thr434Aspfs*13 leading to an altered FX protein were found at heterozygous state in two patients with mild bleeding history.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study showed the feasibility and the interest of high\u2010throughput sequencing approach for rare bleeding disorders, enabling the report of <jats:italic>F10<\/jats:italic> gene screening in a 3\u2010weeks delay, suitable for clinical use. The description of five new variants may contribute to a better understanding of the phenotype\u2010genotype correlation in FX deficiency.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14888","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T08:46:16Z","timestamp":1697445976000},"page":"1565-1572","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Five new <i>F10<\/i> variants in hereditary factor x deficiency detected by high\u2010throughput sequencing"],"prefix":"10.1111","volume":"29","author":[{"given":"C\u00e9dric","family":"Pastoret","sequence":"first","affiliation":[{"name":"Laboratoire d'H\u00e9matologie P\u00f4le de Biologie, CHU de Rennes  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cl\u00e9mentine","family":"Wahl","sequence":"additional","affiliation":[{"name":"Laboratoire d'H\u00e9matologie P\u00f4le de Biologie, CHU de Rennes  Rennes 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