Abstract: Objective　To explore the clinical characteristics and gene variation of severe hereditary von Willebrand disease (VWD) in children. Methods　The clinical data of VWD in 2 children were retrospectively analyzed. The activity of von Willebrand factor (VWF) was detected by immunoturbidimetry. Peripheral blood samples were collected from the patients and their parents. High-throughput gene sequencing was performed to analyze the variation of all exon coding regions and splicing regions of F7, F8, F9, F11 and VWF genes. The variation of VWF gene locus was analyzed by PCR combined with Sanger sequencing. Results　Two boys, aged 1 and 2 years respectively, were clinically characterized by mucocutaneous hemorrhage, and the von Willebrand factor activity (VWF: Act) was <5.0% and <2.8%, respectively. In case 1, the coagulation activity of plasma factor Ⅷ (FⅧ: C) was 1.9%, and the coagulation activity of plasma factor Ⅻ (FⅫ:C) was 43.2%. The FⅧ: C in case 2 was 23%. A homozygous variation of c.813C>G (p.Tyr271Ter) was detected in VWF gene of case 1; both of his parents were heterozygous variation. In case 2, heterozygous variations of c.55G>A (p.Gly19 Arg) and c.1200 C>A (Asp400Glu) were detected in VWF gene, which came from his father and mother, respectively. The c.813C>G (p.Tyr271Ter) variation was associated with type 3 VWD. The mutation rate of c.55G>A (p.Gly19 Arg) was extremely low and was related to type 1 VWD. The mutation of c.1200 C > A (asp400glu) has not been reported, but the software SIFT、Polyphen and MutationTaster all predicted its pathogenicity. Both patients improved after hemostasis and replacement therapy. Conclusion　One case of severe type 1 VWD and one case of severe type 3 severe type 1 VWD were confirmed by gene testing. A new mutation 1200 C>A (Asp400Glu) in VWF gene was found.

Key words: hereditary von Willebrand disease;　pedigree;　hemorrhagic disease;　child