Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): comprehensive genetic analysis by next-generation sequencing of 480 patients
| Autor: | Borràs, Nina, Batlle, Javier, Pérez-Rodríguez, Almudena, López-Fernández, María Fernanda, Rodríguez-Trillo, Ángela, Lourés, Esther, Cid, Ana Rosa, Bonanad, Santiago, Cabrera, Noelia, Moret, Andrés, Parra, Rafael, Mingot-Castellano, María Eva, Balda, Ignacia, Altisent, Carmen, Pérez-Montes, Rocío, Fisac, Rosa María, Iruín, Gemma, Herrero, Sonia, Soto, Inmaculada, de Rueda, Beatriz, Jiménez-Yuste, Víctor, Alonso, Nieves, Vilariño, Dolores, Arija, Olga, Campos, Rosa, Paloma, María José, Bermejo, Nuria, Berrueco, Rubén, Mateo, José, Arribalzaga, Karmele, Marco, Pascual, Palomo Bravo, Ángeles, Sarmiento, Lizheidy, Iñigo, Belén, Nieto Hernández, Maria del Mar, Vidal, Rosa, Martínez, María Paz, Aguinaco, Reyes, César, Jesús María, Ferreiro, María, García-Frade, Javier, Rodríguez-Huerta, Ana María, Cuesta, Jorge, Rodríguez-González, Ramón, García-Candel, Faustino, Cornudella, Rosa, Aguilar, Carlos, Vidal, Francisco, Corrales Insa, Irene, Universitat Autònoma de Barcelona |
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| Rok vydání: | 2017 |
| Předmět: |
Genetic counseling
In silico 030204 cardiovascular system & hematology Bioinformatics Genetic analysis Article 03 medical and health sciences 0302 clinical medicine Von Willebrand factor von Willebrand Factor Von Willebrand disease Humans Medicine Prospective cohort study Genetic Association Studies Hemostasis biology business.industry High-Throughput Nucleotide Sequencing Hematology medicine.disease von Willebrand Diseases Spain Mutation biology.protein Microsatellite business Asymptomatic carrier 030215 immunology |
| Zdroj: | HAEMATOLOGICA r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu instname r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau Universidad Europea (UEM) r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid Haematologica Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu Fundació Sant Joan de Déu |
| ISSN: | 0390-6078 |
| Popis: | Molecular diagnosis of patients with von Willebrand disease is pending in most populations due to the complexity and high cost of conventional molecular analyses. The need for molecular and clinical characterization of von Willebrand disease in Spain prompted the creation of a multicenter project (PCM-EVW-ES) that resulted in the largest prospective cohort study of patients with all types of von Willebrand disease. Molecular analysis of relevant regions of the VWF, including intronic and promoter regions, was achieved in the 556 individuals recruited via the development of a simple, innovative, relatively low-cost protocol based on microfluidic technology and next-generation sequencing. A total of 704 variants (237 different) were identified along VWF, 155 of which had not been previously recorded in the international mutation database. The potential pathogenic effect of these variants was assessed by in silico analysis. Furthermore, four short tandem repeats were analyzed in order to evaluate the ancestral origin of recurrent mutations. The outcome of genetic analysis allowed for the reclassification of 110 patients, identification of 37 asymptomatic carriers (important for genetic counseling) and re-inclusion of 43 patients previously excluded by phenotyping results. In total, 480 patients were definitively diagnosed. Candidate mutations were identified in all patients except 13 type 1 von Willebrand disease, yielding a high genotype-phenotype correlation. Our data reinforce the capital importance and usefulness of genetics in von Willebrand disease diagnostics. The progressive implementation of molecular study as the first-line test for routine diagnosis of this condition will lead to increasingly more personalized and effective care for this patient population. |
| Databáze: | OpenAIRE |
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