Abstract
BACKGROUND: von Willebrand disease (VWD) is the most common inherited bleeding disorder caused by defective or deficient von Willebrand factor (VWF). VWD type 3 is inherited in autosomal recessive manner. We described clinical and molecular features of VWD type 3 in two consanguineous marriage families. METHODS: Peripheral blood was collected, PT, APTT, FVIII:C, VWF:RCo, VWF:Ag were measured. A targeted next-generation sequencing panel covering F8, F9, and VWF genes was applied followed by Sanger sequencing. RESULTS: Both families had a baby die in their first year due to bleeding disorders. A 23-year-old female patient from family A suffered menorrhagia, and another 30-year-old male patient from family B was characterized with hematoma in the lower extremity. Both patients showed severely decreased FVIII:C, VWF:Ag. Recurrent homozygous VWF c.4696C>T (p.Arg1566Ter) nonsense mutation was identified in the female patient, and novel homozygous VWF c.6450C>A (p.Cys2150Ter) nonsense mutation was identified the male patient. Heterozygotes in family members showed mild/moderate decrease in VWF:Ag or VWF:RCo. CONCLUSIONS: We identified VWD type 3 in two consanguineous marriage families, and our work further strengthen the risk of delivering disorders inherited in AR manner in populations with frequent consanguineous partnerships.