{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T15:13:49Z","timestamp":1770995629823,"version":"3.50.1"},"reference-count":103,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T00:00:00Z","timestamp":1631059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Asociaci\u00f3n Andaluza de Hemofilia","award":["FV2016-2021"],"award-info":[{"award-number":["FV2016-2021"]}]},{"DOI":"10.13039\/501100016300","name":"Octapharma","doi-asserted-by":"publisher","award":["OCT-2020-21"],"award-info":[{"award-number":["OCT-2020-21"]}],"id":[{"id":"10.13039\/501100016300","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Factor V is an essential clotting factor that plays a key role in the blood coagulation cascade on account of its procoagulant and anticoagulant activity. Eighty percent of circulating factor V is produced in the liver and the remaining 20% originates in the \u03b1-granules of platelets. In humans, the factor V gene is about 80 kb in size; it is located on chromosome 1q24.2, and its cDNA is 6914 bp in length. Furthermore, nearly 190 mutations have been reported in the gene. Factor V deficiency is an autosomal recessive coagulation disorder associated with mutations in the factor V gene. This hereditary coagulation disorder is clinically characterized by a heterogeneous spectrum of hemorrhagic manifestations ranging from mucosal or soft-tissue bleeds to potentially fatal hemorrhages. Current treatment of this condition consists in the administration of fresh frozen plasma and platelet concentrates. This article describes the cases of two patients with severe factor V deficiency, and of their parents. A high level of mutational heterogeneity of factor V gene was identified, nonsense mutations, frameshift mutations, missense changes, synonymous sequence variants and intronic changes. These findings prompted the identification of a new mutation in the human factor V gene, designated as Ja\u00e9n-1, which is capable of altering the procoagulant function of factor V. In addition, an update is provided on the prospects for the treatment of factor V deficiency on the basis of yet-to-be-developed recombinant products or advanced gene and cell therapies that could potentially correct this hereditary disorder.<\/jats:p>","DOI":"10.3390\/ijms22189705","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T10:12:03Z","timestamp":1631095923000},"page":"9705","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["High Mutational Heterogeneity, and New Mutations in the Human Coagulation Factor V Gene. Future Perspectives for Factor V Deficiency Using Recombinant and Advanced Therapies"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4427-0574","authenticated-orcid":false,"given":"Sara","family":"Bernal","sequence":"first","affiliation":[{"name":"Department of Genetics, Santa Creu i Sant Pau Hospital and IIB Sant Pau, 08041 Barcelona, Spain"},{"name":"CIBERER. U-705, 18014 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Pelaez","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Oncohematology, University Hospital Virgen de las Nieves, 18014 Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Alias","sequence":"additional","affiliation":[{"name":"Department of Genetics, Santa Creu i Sant Pau Hospital and IIB Sant Pau, 08041 Barcelona, Spain"},{"name":"CIBERER. U-705, 18014 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manel","family":"Baena","sequence":"additional","affiliation":[{"name":"Department of Genetics, Santa Creu i Sant Pau Hospital and IIB Sant Pau, 08041 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9491-5572","authenticated-orcid":false,"given":"Juan A.","family":"De Pablo-Moreno","sequence":"additional","affiliation":[{"name":"Department of Genetic, Physiology and Microbiology, School of Biology, Complutense University, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0363-3148","authenticated-orcid":false,"given":"Luis J.","family":"Serrano","sequence":"additional","affiliation":[{"name":"Department of Genetic, Physiology and Microbiology, School of Biology, Complutense University, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Dolores","family":"Camero","sequence":"additional","affiliation":[{"name":"Association for the Investigation and Cure of Factor V Deficiency, 23002 Ja\u00e9n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo F.","family":"Tizzano","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Genetics, University Hospital Vall d\u2019Hebron and Medicine Genetics Group, Vall d\u2019Hebron Research Institute, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruben","family":"Berrueco","sequence":"additional","affiliation":[{"name":"Pediatric Hematology Department, Hospital Sant Joan de D\u00e9u, University of Barcelona and Research Institute Hospital Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Liras","sequence":"additional","affiliation":[{"name":"Department of Genetic, Physiology and Microbiology, School of Biology, Complutense University, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1055\/s-0039-1687906","article-title":"A Comprehensive Overview of Coagulation Factor V and Congenital Factor V Deficiency","volume":"45","author":"Tabibian","year":"2019","journal-title":"Semin. 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