Molecular diagnosis of von Willebrand disease

Abstract

word count: 212 Text word count: 3781Number of Tables and Figures: Tables 3, Figures 3 2 AbstractThe role of molecular characterization in the diagnosis of VWD is not essential if the patients have been extensively investigated using phenotypic analysis. On the other hand, if some of these phenotype assays are not available, the identification of the mutation causing the disease could be crucial for an accurate diagnosis. Nevertheless, there are several reasons for performing molecular analysis in patients phenotypically well characterized, e.g. to identify the mutation causing VWD can be useful for patients and their family members when prenatal diagnosis is required (type 3 or severe type 2).In this manuscript we report the techniques used for the molecular characterization of suspected VWD patients. We describe the use of online VWF database and online SNV (single nucleotide variation) databases, the former to verify whether a candidate mutation has been previously identified in other VWD patients and the latter to ascertain whether a putative mutation has been reported earlier in healthy individuals. We listed the available in silico analysis tools, to determine the predicted pathogenicity of a sequence variant and to establish its possible negative effect on the normal splicing process. We also report the strategy that can be used to identify VWD type 2 patients' mutations in subjects that have been fully characterized using the phenotype assays.

Genetic Background of von Willebrand Disease: History, Current State, and Future Perspectives

“…After translocation into endoplasmic reticulum (ER), the signal peptide is cleaved and the pro-VWF dimerizes through disulfide bridges between the cysteine residues of Cterminal CK domain. 15,20 Using current numbering system, the initiating methionine codon is defined as nucleotide number 1, and this methionine is also identified as amino acid number 1. Information on potential regulatory elements of VWF includes the analysis of 2.2-kb upstream sequence.…”

Von Willebrand disease as a significant risk factor for hemorrhage after cervical loop electrosurgical excision

“…7 It is still a priority to focus on the particular patient and evaluate the signs and symptoms of the disease. There is a strong evidence that diagnosis of this condition is demanded to be over-and underdetected because of clinical misperception of actual prevalence of vWD.…”

¿Qué avances recientes hay en el entendimiento, diagnóstico y tratamiento de la enfermedad de Von Willebrand?: una revisión de la literatura

“…Existe, además, un seudogen con copia de los exones 23 al 34 en el cromosoma 22. Codifica para ARNm de 8,8 Kb de longitud, su proteína constituye una glucoproteína plasmática de entre 500 y 2000 KDa, posee 2813 aminoácidos, de los cuales 22 equivalen a un péptido señal, 741 a un propolipéptido (dominios D1 y D2) y 2050 a la subunidad del FVW con propiedades adhesivas necesarias para cumplir su función hemostática (18,19). Se han descrito 140 polimorfismos de inserción y deleción ubicados en su región promotora, regiones intrónicas y exones (6,20,21).…”