Open AccessTwo cases of von Willebrand disease type 3 in consanguineous Chinese families
Author(s) -
Wang Xiong,
Tang Ning,
Lu Yanjun,
Hu Qun,
Li Dengju
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1075
Subject(s) - von willebrand disease , sanger sequencing , von willebrand factor , medicine , consanguinity , compound heterozygosity , nonsense mutation , family history , consanguineous marriage , pediatrics , nonsense , heterozygote advantage , genetics , mutation , genotype , gene , missense mutation , biology , platelet
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.