Caracterización de variantes en el exón 28 del gen VWF y su correlación genotipo-fenotipo en una muestra de pacientes con enfermedad de Von Willebrand tipo 2

Introduction Von Willebrand's disease is the most common hereditary coagulopathy in the population, the approach of molecular analysis as diagnostic support has been little EvW type 2. The aim of this study is to characterize variants in exon 28 of the VWF gene and to perform genotype-phenotype correlation in a sample of patients with type 2 VWD. Methos: 20 samples from patients previously diagnosed with VWD were analyzed. Von Willebrand disease type 2 with ages between 8 and 56 years. Analysis of Exon 28 of the VWF gene was performed, by amplification, verification by electrophoresis in agarose gels and sequencing with the Big Dye Terminator V3.1 Kit. Results: The pathogenic variant was identified in 15 (88.2%) unrelated patients. The p.Gly1609Arg variant was identified in 52.9% of the patients analyzed (n=9) alone or in combination, followed in frequency by p.Ile1425Phe (n=3), and p.Ala1437Thr (n=3) alone or in combination, 1 patient with p.Arg1597Trp and another with p.Arg1334Trp. Additionally, two pathogenic variants were identified in 31.6% (n=6) of patients (2 patients with p.Gly1609Arg/p.Ala1437Thr; 1 patient p.Gly1609Arg/p.Ser1506Leu; 1 patient p.Gly1609Arg/p.Arg1597Trp; 1 patient p.Gly1609Arg/p.Val1279Phe; and 1 patient p.Ile1628Thr/p.Ser1325Phe). No variant was identified in 2 patients (11.8%). It was possible to reclassify the EvW type 2 subtype in 40% (n=8) of patients. Conclusions: This is the first study performed in the country, which allowed the identification of the genetic cause of EvW for the first time in Colombia by sequencing specific exons in a follow-up cohort.