Akademik Veri Yönetim Sistemi
EAHAD 2024, Frankfurt, Almanya, 6 - 09 Şubat 2024, cilt.30, ss.127-128
B. Koc1,*; S. Kılıc Erciyas2; B. Tuncer2; B. Zulfikar1
1Department of Pediatric Hematology/Oncology; 2Basic Oncology, Department of Cancer Genetics, Istanbul University Oncology Institute, Istanbul, Türkiye
Introduction: Genetic variations affect the plasma level and function of the von Willebrand factor (vWF), resulting in impaired haemostasis. There are difficulties in diagnosing and determining the type of disease. The objective of the present study is to evaluate the genetic variations who are diagnosed with von Willebrand disease (vWD) Type2 or who have differences in typing in the same patients due to laboratory differences, and the impact of these variations on the clinical phenotypes.
Methods: Eighteen patients were enrolled. Demographic and clinical data for all patients, Bleeding Assessment Tool (BAT) scores and blood samples for genetic analysis were collected. DNA samples extracted from the patient's blood samples were sequenced using the Twist HC Exome Panel.
Results: The median age of the patients was 21.5 years (range: 5–54), with 13 females. The median BAT score was 9 (range: 7–21). All patients except one had a family history. Following WES analysis, data for 551,654 variants in 21,560 genes were obtained: 39.07% of the variants/mutations obtained are synonymous, 37.44% are missense, 8% are intronic, 4.39% are intergenic, 0.86% are splice donor/acceptor, 0.78% are frameshift, 0.33% consist of nonsense mutations and others. According to the initial pathogenicity prediction classification, %0.008 is classified as group A (pathogenic), %1.79 is classified as group B (likely pathogenic), %14.5 is classified as group C (uncertain significance) and %83.7 is classified as group D (likely benign, benign or no clinical significance) variants. Among the analysed results, when examined in terms of genes directly related to bleeding, three patients (from the same family) were found to carry one pathogenic mutation in the F8 gene, six patients (from five different families) had five different mutations in the VWF gene and one patient was found to carry one pathogenic mutation in F9 gene. Three patients with F8 mutations and two patients with VWF mutations belonged to the same family.
Discussion/Conclusion: The diagnosis of VWD still presents challenges. Our findings suggest that genetic testing holds promise for cases initially suspected to be VWD. In this investigation, the identified F8, F9 and VWF mutations elucidated the aetiology of bleeding symptoms in the 10 patients participating in the study. This study remains ongoing, we anticipate further updates and new data will continue to be obtained.