High Mutational Heterogeneity, and New Mutations in the Human Coagulation Factor V Gene. Future Perspectives for Factor V Deficiency Using Recombinant and Advanced Therapies
| Autor: | Irene Pelaez, Antonio Liras, Juan Andres De Pablo-Moreno, Eduardo F. Tizzano, M. Dolores Camero, Luis J. Serrano, Sara Bernal, Laura Alias, Rubén Berrueco, Manel Baena |
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| Přispěvatelé: | Institut Català de la Salut, [Bernal S, Alias L] Department of Genetics, Santa Creu i Sant Pau Hospital and IIB Sant Pau, 08041 Barcelona, Spain. CIBERER. U-705, 18014 Barcelona, Spain. [Pelaez I] Department of Pediatric and Oncohematology, University Hospital Virgen de las Nieves, 18014 Granada, Spain. [Baena M] Department of Genetics, Santa Creu i Sant Pau Hospital and IIB Sant Pau, 08041 Barcelona, Spain. [De Pablo-Moreno JA, Serrano LJ] Department of Genetic, Physiology and Microbiology, School of Biology, Complutense University, 28040 Madrid, Spain. [Tizzano EF] Servei de Genètica Clínica i Molecular, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Grup de Recerca en Genètica de la Medicina, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus |
| Rok vydání: | 2021 |
| Předmět: |
Male
Advanced therapies Owren’s disease Parahemophilia DNA Mutational Analysis técnicas de investigación::técnicas genéticas::análisis de secuencias::análisis de secuencias de ADN::análisis de mutaciones del ADN [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Missense mutation Platelet Pakistan Biology (General) Frameshift Mutation Otros calificadores::/terapia [Otros calificadores] Spectroscopy Coagulation Disorder Clotting factor advanced therapies enfermedades hematológicas y linfáticas::enfermedades hematológicas::trastornos de la coagulación sanguínea::trastornos de la coagulación sanguínea hereditarios::deficiencia del factor V [ENFERMEDADES] biology Factor V General Medicine Recombinant Proteins Computer Science Applications Chemistry Mutation analysis Factor V deficiency Codon Nonsense Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis DNA::DNA Mutational Analysis [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] Child Preschool Sang - Coagulació - Trastorns Female Blood Coagulation Tests Amino Acids Peptides and Proteins::Proteins::Recombinant Proteins [CHEMICALS AND DRUGS] Blood Platelets factor V deficiency Factor V Deficiency DNA Complementary Adolescent QH301-705.5 aminoácidos péptidos y proteínas::proteínas::proteínas recombinantes [COMPUESTOS QUÍMICOS Y DROGAS] Nonsense mutation Catalysis Article Frameshift mutation Inorganic Chemistry Blood Coagulation Disorders Inherited Proteïnes recombinants Owren's disease Humans Physical and Theoretical Chemistry Molecular Biology QD1-999 Blood Coagulation mutation analysis Seqüència de nucleòtids Family Health Hemic and Lymphatic Diseases::Hematologic Diseases::Blood Coagulation Disorders::Blood Coagulation Disorders Inherited::Factor V Deficiency [DISEASES] Organic Chemistry Other subheadings::/therapy [Other subheadings] Sequence Analysis DNA Genética parahemophilia Spain biology.protein Cancer research |
| Zdroj: | International Journal of Molecular Sciences E-Prints Complutense. Archivo Institucional de la UCM instname International Journal of Molecular Sciences, Vol 22, Iss 9705, p 9705 (2021) INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau Volume 22 Issue 18 Scientia |
| ISSN: | 1422-0067 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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