Abstract
Inherited bleeding disorders (IBDs) are the most frequent congenital diseases in the Colombian population; three of them are hemophilia A (HA), hemophilia B (HB), and von Willebrand Disease (VWD). Currently, diagnosis relies on multiple clinical laboratory assays to assign a phenotype. Due to the lack of accessibility to these tests, patients can receive an incomplete diagnosis. In these cases, genetic studies reinforce the clinical diagnosis. The present study characterized the molecular genetic basis of 11 HA, three HB, and five VWD patients by sequencing the F8, F9, or the VWF gene. Twelve variations were found in HA patients, four in HB patients, and 19 in WVD patients. From these variations a total of 25 novel variations were found. Disease-causing variations were used as positive controls for validation of the high-resolution melting (HRM) variant-scanning technique. This approach is a low-cost genetic diagnostic method proposed to be incorporated in developing countries. For the data analysis, we developed an accessible open-source code in Python that improves HRM data analysis with better sensitivity of 95% and without bias when using different HRM equipment and software. Analysis of amplicons with a length greater than 300 bp can be performed by implementing an analysis by denaturation domains.
Highlights
Inherited bleeding disorders (IBDs) are a group of conditions where deficiencies in plasma proteins, involved in blood coagulation, lead to increased risk of bleeding [1]
Hemophilia A (HA), hemophilia B (HB), and von Willebrand Disease (VWD) are the most common IBDs associated with a lack of clotting factors (blood coagulation factor VIII (F8), factor IX (F9), and von Willebrand factor (VWF), respectively)
Data sourced from the World Bank Group show that 2639 individuals are diagnosed with HA, 591 with HB, and 2770 with VWD in Colombia
Summary
Inherited bleeding disorders (IBDs) are a group of conditions where deficiencies in plasma proteins, involved in blood coagulation, lead to increased risk of bleeding [1]. Hemophilia A (HA), hemophilia B (HB), and von Willebrand Disease (VWD) are the most common IBDs associated with a lack of clotting factors (blood coagulation factor VIII (F8), factor IX (F9), and von Willebrand factor (VWF), respectively). Unclear diagnosis in many cases may occur, as test results suffer from extreme variability, in part because of the wide range of methods, reagents, and instruments, and the lack of access to genetic testing [5] This is evidenced by the differences in reports of prevalence. According to the report from the high-cost account published in Colombia in 2019 [6], 1916 individuals are diagnosed with HA, 415 with HB, and 1444 with VWD These data suggest the lack of clarity in the exact prevalence in the country and exemplify the need to implement genetic studies that support a more precise diagnosis. Healthcare resources can be better managed and allocated [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
