High mutational heterogeneity, and new mutations in the human coagulation factor v gene. Future perspectives for factor v deficiency using recombinant and advanced therapies
Bernal, Sara (Institut d'Investigació Biomèdica Sant Pau)
Pelaez, Irene (Hospital Universitario Virgen de las Nieves (Granada))
Alías, Laura (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Baena, Manel (Institut d'Investigació Biomèdica Sant Pau)
Pablo-Moreno, Juan A.D. (Department of Genetic. Physiology and Microbiology. School of Biology. Complutense University)
Serrano, Luis J. (Department of Genetic. Physiology and Microbiology. School of Biology. Complutense University)
Camero, Maria Dolores (Association for the Investigation and Cure of Factor V Deficiency)
Tizzano, Eduardo F. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Berrueco, Rubén (Institut de Recerca Sant Joan de Déu)
Liras, Antonio (Department of Genetic. Physiology and Microbiology. School of Biology. Complutense University)

Data:	2021
Resum:	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 α-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 Jaén-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.
Nota:	Altres ajuts: Asociación Andaluza de Hemofilia
Nota:	Altres ajuts: Octapharma S.A. OCPH-2019-20
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Factor V deficiency ; Parahemophilia ; Owren's disease ; Mutation analysis ; Advanced therapies
Publicat a:	International journal of molecular sciences, Vol. 22 Núm. 18 (september 2021) , p. 9705, ISSN 1422-0067

DOI: 10.3390/ijms22189705
PMID: 34575869

22 p, 2.4 MB

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