Genetic variants in VWF exon 26 and their implications for type 1 Von Willebrand disease in a Saudi Arabian population.

Von Willebrand disease (VWD) is one of the most common bleeding disorders, stemming from irregularities in the Von Willebrand factor (VWF). Globally, type 1 VWD (VWD1) is the most prevalent form, characterized by decreased levels of VWF in the blood. Genotyping studies have found causative genetic variants in approximately 65% of VWD1 cases, revealing the presence of ethnic-specific VWF variants. This study is limited by its exclusive focus on exon 26, warranting further investigation of other exons and the inclusion of functional analyses. Moreover, these findings emphasize the importance of understanding genetic variability in population-specific contexts, supporting the necessity for future studies on additional exons and potential epigenetic interactions. Between 2018 and 2019, samples and relevant medical data were collected at King Fahad Hospital of the University in Al Khobar. Sanger sequencing of the exonic and flanking intronic regions of exon 26 was performed on 22 index cases clinically diagnosed with VWD1 and their first-degree relatives. Analysis revealed four exonic and 11 intronic variants in VWF exon 26 among the participants. None of the identified variants appeared to explain the VWD-related clinical features in these individuals. However, findings suggest a higher prevalence of specific VWF variants within the Saudi population compared to global databases. Further investigation, including sequencing of additional exons or next-generation sequencing, may help to uncover potential disease-causing variants in this cohort. Establishing a national sequencing project could also enhance our understanding of both common and rare variants in the genetic basis of complex diseases, such as VWD1.