Molecular and clinical profile of type 2 von Willebrand disease in Iran: a thirteen-year experience

Type 2 von Willebrand disease (VWD) is the most common congenital bleeding disorder, with variable bleeding tendency and a complex laboratory phenotype. In the current study, we report the clinical and molecular profile of a large number of Iranian patients with type 2 VWD. All exons, intron�exon boundaries, and untranslated regions were sequenced by Sanger sequencing for direct mutation detection. All identified mutations were confirmed in family members and by relevant bioinformatics studies. A total of 136 patients with type 2 VWD were diagnosed, including 42 (30.9), 32 (23.6), 38 (27.9), and 24 (17.6) patients with type 2A, type 2B, type 2M, and type 2N, respectively. Epistaxis (49), gum bleeding (30.2), ecchymosis (23.2), and menorrhagia (16.3) were the most common clinical presentations, while miscarriage (2.3) and umbilical cord bleeding (0.8) were the rarest. Thirty mutations were identified within the VWF gene, nine (30) being novel, with p.Arg1379Cys (n = 20), p.Val1316Met (n = 13), p.Arg1597Trp (n = 13), p.Arg1374Cys (n = 10), p.Ser1506Leu (n = 10), and p.Arg1308Cys (n = 9) the most common. Type 2 VWD is a hemorrhagic disorder with variable bleeding tendency and a heterogeneous molecular basis in patients in Iran. © 2020, Japanese Society of Hematology