RT Journal Article
T1 Molecular and clinical profile of von Willebrand disease in Spain (PCM-EVW-ES): comprehensive genetic analysis by next-generation sequencing of 480 patients.
A1 Borràs, Nina
A1 Batlle, Javier
A1 Pérez-Rodríguez, Almudena
A1 López-Fernández, María Fernanda
A1 Rodríguez-Trillo, Ángela
A1 Lourés, Esther
A1 Cid, Ana Rosa
A1 Bonanad, Santiago
A1 Cabrera, Noelia
A1 Moret, Andrés
A1 Parra, Rafael
A1 Mingot-Castellano, María Eva
A1 Balda, Ignacia
A1 Altisent, Carme
A1 Pérez-Montes, Rocío
A1 Fisac, Rosa María
A1 Iruín, Gemma
A1 Herrero, Sonia
A1 Soto, Inmaculada
A1 de Rueda, Beatriz
A1 Jiménez-Yuste, Víctor
A1 Alonso, Nieves
A1 Vilariño, Dolores
A1 Arija, Olga
A1 Campos, Rosa
A1 Paloma, María José
A1 Bermejo, Nuria
A1 Berrueco, Rubén
A1 Mateo, José
A1 Arribalzaga, Karmele
A1 Marco, Pascual
A1 Palomo, Ángeles
A1 Sarmiento, Lizheidy
A1 Iñigo, Belén
A1 Nieto, María Del Mar
A1 Vidal, Rosa
A1 Martínez, María Paz
A1 Aguinaco, Reyes
A1 César, Jesús María
A1 Ferreiro, María
A1 García-Frade, Javier
A1 Rodríguez-Huerta, Ana María
A1 Cuesta, Jorge
A1 Rodríguez-González, Ramón
A1 García-Candel, Faustino
A1 Cornudella, Rosa
A1 Aguilar, Carlos
A1 Vidal, Francisco
A1 Corrales, Irene
AB 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.
YR 2017
FD 2017-09-29
LK http://hdl.handle.net/10668/11640
UL http://hdl.handle.net/10668/11640
LA en
DS RISalud
RD Apr 18, 2025