Molecular and clinical profile of von willebrand disease in spain (PCM-EVW-ES): Proposal for a new diagnostic paradigm
| Autor: | Esther Lourés, María del Mar Nieto, L. Sarmiento, Rafael Parra, Jorge Cuesta, O. Arija, Javier Batlle, Faustino García-Candel, Víctor Jiménez-Yuste, J. M. César, Ana María Rodríguez-Huerta, Rosa Vidal, Karmele Arribalzaga, Rosa Campos, María Paz Martínez, Ramón Rodríguez-González, Francisco Vidal, Sonia Herrero, Nuria Bermejo, María Ferreiro, Almudena Pérez-Rodríguez, R. Cornudella, Javier García-Frade, Maria Eva Mingot-Castellano, Rosa Fisac, Ángela Rodríguez-Trillo, Pascual Marco, I. Balda, Ana Rosa Cid, Reyes Aguinaco, D. Vilariño, Irene Corrales, T. Toll, José Mateo, Ángeles Palomo, N. Cabrera, Santiago Bonanad, María Fernanda López-Fernández, Nieves Alonso, Belén Iñigo, Andrés Moret, Inmaculada Soto, Rocío Pérez-Montes, Nina Borràs, Gemma Iruin, B. de Rueda, Carlos Aguilar, María José Paloma, Carmen Altisent |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Genetic Markers
Male medicine.medical_specialty congenital hereditary and neonatal diseases and abnormalities phenotype genotype DNA Mutational Analysis 030204 cardiovascular system & hematology Bioinformatics 03 medical and health sciences 0302 clinical medicine Von Willebrand factor Predictive Value of Tests Risk Factors Internal medicine hemic and lymphatic diseases von Willebrand Factor Genotype medicine Von Willebrand disease Humans VWF Genetic Predisposition to Disease Registries Genetic Association Studies VWD Molecular Epidemiology biology Case-control study High-Throughput Nucleotide Sequencing Hematology NGS VWD VWF genotype phenotype medicine.disease Phenotype von Willebrand Diseases Spain Case-Control Studies Predictive value of tests NGS Mutation Cohort biology.protein Female Leiden Open Variation Database 030215 immunology |
| Zdroj: | THROMBOSIS AND HAEMOSTASIS r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu Fundació Sant Joan de Déu r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu Thrombosis and haemostasis r-FISABIO: Repositorio Institucional de Producción Científica Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO) r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe r-FISABIO. Repositorio Institucional de Producción Científica r-ISABIAL. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica y Sanitaria de Alicante |
| ISSN: | 0340-6245 |
| Popis: | SummaryThe diagnosis of von Willebrand disease (VWD) remains difficult in a significant proportion of patients. A Spanish multicentre study investigated a cohort of 556 patients from 330 families who were analysed centrally. VWD was confirmed in 480. Next generation sequencing (NGS) of the whole coding VWF was carried out in all recruited patients, compared with the phenotype, and a final diagnosis established. A total of 238 different VWF mutations were found, 154 were not included in the Leiden Open Variation Database (LOVD). Of the patients, 463 were found to have VWF mutation/s. A good phenotypic/ genotypic association was estimated in 96.5 % of the patients. One hundred seventy-four patients had two or more mutations. Occasionally a predominant phenotype masked the presence of a second abnormality. One hundred sixteen patients presented with mutations that had previously been associated with increased von Willebrand factor (VWF) clearance. RIPA unavailability, central phenotypic results disagreement and difficult distinction between severe type 1 and type 3 VWD prevented a clear diagnosis in 70 patients. The NGS study facilitated an appropriate classification in 63 of them. The remaining seven patients presented with a VWF novel mutation pending further investigation. In five patients with a type 3 and two with a type 2A or 2B phenotype with no mutation, an acquired von Willebrand syndrome (AVWS) was suspected/confirmed. These data seem to support NGS as a first line efficient and faster paradigm in VWD diagnosis.Supplementary Material to this article is available online at www.thrombosis-online.com. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|