Study on pathogenesis and laboratory diagnosis of a family with von Willebrand disease caused by c.1117C＞T/c.7288-9T＞G compound heterozygous mutation / 临床检验杂志

ABSTRACT

Objective To explore the diagnosis of clinically suspicious von Willebrand disease(vWD)in a family and its pathogene-sis.Methods The pedigree information and the biological specimen were collected from the clinically suspected VWD patient and her family members(4 persons in total)in Peking University First Hospital.The levels of platelet count(PLT),activated partial thrombo-plastin time(APTT),vWF antigen(vWFAg),vWF activity(vWFAc)and FⅧ activity(FⅧC)were detected,and vWF risto-cetin cofactor(vWFRCo)assay,ristocetin-induced platelet aggregation assay(RIPA)and vWF collagen binding(vWFCB)assay were performed for phenotype diagnosis.The peripheral blood genomic DNAs were extracted from the proband and her family members to perform whole-exome sequencing for identifying the mutation of vWF gene,The mutation site was analyzed by using bioinformation tools to explore the pathogenesis of the proband.Results The APTT of proband(m 1)was slightly prolonged and her vWFAg,vWFAc,vWFRCo and vWFCB were significantly decreased.There was no obvious aggregation in RIPA assay(1.0 mg/mL and 1.25 mg/mL).In her father(Ⅱ3),APTT,FⅧC,vWFAg,vWFAc and vWFCB were normal,but vWFRCo was slightly decreased.In her mother(Ⅱ4),APTT,FⅧC,vWFAg,vWFRCo and vWFCB were all normal,but vWFAc significantly decreased.In her brother(Ⅲ2),APTT and FⅧC were normal,but vWFAg,vWFAc,vWFRCo and vWFCB were reduced to varying degrees.In all the family members(father,mother and brpther),no apparent aggregation in RIPA(1.0 mg/mL)was shown.Genetic analysis showed that the proband(Ⅲ1)carried a compound heterozygous mutation of vWF gene c.7288-9T＞G and c.1117C＞T,her father(Ⅱ3)carried vWF gene c.7288-9T＞G heterozygous mutation,and vWF gene c.1117C＞T heterozygous mutation was presented in both mother(Ⅱ4)and brother(Ⅲ2).Conclusion According to the results of laboratory tests,the proband was diagnosed as type 2A vWD.The hetero-zygous mutation in vWF gene c.1117C＞T and c.7288-9T＞G may be the molecular mechanism leading to type 2A vWD in the proband.