title: The significance of F139V mutation on thrombotic events in compound heterozygous and homozygous protein C deficiency.
abstract: 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.
authors.affiliation: aClinical Laboratory Diagnostic Centre bDepartment of haematology cDepartment of Surgery, Wenzhou Key Laboratory of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
authors.forename: Li-hong
authors.initials: LH
authors.lastname: Yang
authors.forename: Fang-xiu
authors.initials: FX
authors.lastname: Zheng
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Yan-hui
authors.initials: YH
authors.lastname: Jin
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Hai-xiao
authors.initials: HX
authors.lastname: Xie
authors.forename: Xiao-li
authors.initials: XL
authors.lastname: Yang
authors.forename: Ming-shan
authors.initials: MS
authors.lastname: Wang
authors.forename: Bi-cheng
authors.initials: BC
authors.lastname: Chen
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D005091:Exons; D005165:Factor V / Q000378:metabolism; D005169:Factor VIII / Q000378:metabolism; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010314:Partial Thromboplastin Time; D010375:Pedigree; D011486:Protein C / Q000235:genetics* / Q000378:metabolism; D020151:Protein C Deficiency / Q000097:blood / Q000235:genetics*; D011517:Prothrombin Time; D017422:Sequence Analysis, DNA; D013918:Thrombin Time; D013927:Thrombosis / Q000097:blood / Q000235:genetics*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D011486:Protein C; C036309:fibrin fragment D; D005165:Factor V; D005169:Factor VIII; D005340:Fibrinogen