The significance of F139V mutation on thrombotic events in compound heterozygous and homozygous protein C deficiency
| Autor: | Mingshan Wang, Lihong Yang, Zhuo Zhang, Yi Chen, Bi-cheng Chen, Haixiao Xie, Fang-xiu Zheng, Yanhui Jin, Xiao-li Yang |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Heterozygote Thrombin Time Molecular Sequence Data Compound heterozygosity medicine.disease_cause Fibrin Fibrinogen Degradation Products Exon medicine Missense mutation Humans Allele Alleles Mutation Factor VIII biology Base Sequence Chemistry Homozygote Factor V Fibrinogen Protein C Deficiency Heterozygote advantage Thrombosis Hematology General Medicine Exons Sequence Analysis DNA Molecular biology Pedigree biology.protein Prothrombin Time Female Partial Thromboplastin Time Protein C medicine.drug |
| Zdroj: | Blood coagulationfibrinolysis : an international journal in haemostasis and thrombosis. 25(8) |
| ISSN: | 1473-5733 |
| Popis: | Both compound heterozygous and homozygous protein C deficiencies (PCDs) can cause lethal thrombotic events in children. This study investigated the significance of F139V mutation in activation of protein C in heterozygous and biallelic PCD. Two pedigrees with three probands were recruited, including heterozygous, compound heterozygous, and homozygous PCD and non-PCD families. The plasma levels of protein C activity (PC:A), protein C antigen (PC:Ag), factor V:C, factor VIII:C, fibrinogen (FIB), and D-dimer (D-D) were measured. Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were also detected. All nine exons of protein C gene (PROC) were sequenced. Protein C mutation, T>G at site 6128 (exon 7) resulting in F139V, was identified in both pedigrees. Heterozygous missense mutation F139V (n = 10) had 56.4% lower levels of PC:A and PC:Ag compared with members with wild-type PROC (n = 6). Biallelic compound heterozygous and homozygous PCDs with F139V (n = 3) significantly decreased the levels of PC:A and PC:Ag compared with heterozygous members (P < 0.05); however, these were not lethal. Heterozygous F139V mutations of PRO caused mild reduction of protein C function, which might be the reason for survival of compound heterozygous or homozygous PCD with F139V in adults. |
| Databáze: | OpenAIRE |
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