Identification of Diagnostic SNPs in Exon ۲۸ of the Von Willebrand Factor Gene for Diagnosis of VWD Type ۲B in Patients Referred to IBTO Coagulation Lab: In-silico Approach

Background and Aims: von Willebrand disease (VWD) is brought on by hereditary impairments in the von Willebrand factor (VWF). It has been determined that most of the molecular abnormalities are present in exon ۲۸ of the VWF gene qualitative variations. In this regard, investigating mutations in exon ۲۸ of the VWF coding gene can help identify the VWD type and can be used to manage patients by using appropriate strategies. Materials and Methods: ۱۰ suspected VWD type ۲B patients were investigated for the genotype of exon ۲۸. Routine coagulation tests were performed for the patients. Molecular sequencing was also used for the evaluation of mutations in exon ۲۸. Determining the tertiary structure of VWF can aid in understanding its functional residues and interactions. The nsSNVs’ pathogenicity was examined utilizing potent bioinformatics methods. Step-by-step testing of the high-risk mutations was done using SIFT, PolyPhen-۲, I-Mutant ۲.۰, PHD-SNPg, and SNPs&GO. Then, the secondary structure, amino acid conservation, and feature of amino acids were investigated via Protparam, Cofactor, Interprosurf, ConSurf, NetSurfP-۲.۰, and HOPE. Results: N۱۲۳۱T, V۱۲۲۹G, V۱۳۱۶M, and P۱۲۶۶Q missense mutations in VWF were detected. ۳D structure of VWF predicted and evaluated. Putative conserved domains were identified. P۱۲۶۶Q and V۱۳۱۶M amino acid substitutions are predicted as “Not tolerated substitution” damaging and Disease, while V۱۲۲۹G and N۱۲۳۱T amino acid substitutions are predicted as “tolerated substitution” benign and Neutral. Conclusion: V۱۳۱۶M and P۱۲۶۶Q amino acid substitutions were determined as high-risk mutations using powerful bioinformatics tools in VWD patients.

کلیدواژه ها:

In-silico ، Single nucleotide polymorphism ، Von Willebrand factor ، بیوانفورماتیک ، بیماری فون ویلبراند ، فاکتور فون ویلبراند