title: [Genotype and function analyses of four inherited dysfibrinogenemia pedigree caused by Arg16 amino acid substitution in fibrinogen Aα chain].
abstract: OBJECTIVE
  To analyze the phenotype, genotype and function in four Chinese pedigrees with inherited dysfibrinogenemia.
  
  
  METHODS
  Routing tests including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), reptilase time (RT), the activities of antithrombin (AT), protein C (PC) and protein S (PS) were detected in four pedigrees. The activity and antigen of plasma fibrinogen were analyzed by Clauss and immunoturbidimetry methods, respectively. The molecular weight of fibrinogen of four probands was assessed by Western blot. The function of abnormal fibrinogen was evaluated by fibrinogen clottability, fibrinogen dynamic polymerization and fibrinolysis velocity, respectively. The sequences of all the exons and exon-intron boundaries of the three fibrinogen genes were amplified by PCR and analyzed by direct sequencing.
  
  
  RESULTS
  Four probands had prolonged TT and RT, reduced plasma fibrinogen activity levels and normal antigen levels. The assays of Western blot showed no abnormal molecular weight of fibrinogen. Function tests revealed reduced fibrinogen clottability, delayed and decreased fibrinogen dynamic polymerization and reduced fibrinolysis velocity. Aα chain Arg16His and Arg16Cys mutations were identified in the four probands, respectively.
  
  
  CONCLUSIONS
  The four probands with dysfibrinogenemia were caused by the mutations of Aα chain Arg16His or Arg16Cys. Mutation of the fibrinogen induced dysfunction of plasma fibrinogen.
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Rui-jin Hospital Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Lin-lin
authors.initials: LL
authors.lastname: Jiang
authors.forename: Xue-feng
authors.initials: XF
authors.lastname: Wang
authors.forename: Qiu-lan
authors.initials: QL
authors.lastname: Ding
authors.forename: Guan-qun
authors.initials: GQ
authors.lastname: Xu
authors.forename: Li-wei
authors.initials: LW
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Dai
authors.forename: Ye-ling
authors.initials: YL
authors.lastname: Lu
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: Xi
authors.forename: Hong-li
authors.initials: HL
authors.lastname: Wang
mesh_terms: D000328:Adult; D000347:Afibrinogenemia / Q000097:blood* / Q000235:genetics*; D001780:Blood Coagulation Tests; D005260:Female; D005340:Fibrinogen / Q000235:genetics; D015241:Fibrinogens, Abnormal / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D013918:Thrombin Time
chemical_list: D015241:Fibrinogens, Abnormal; D005340:Fibrinogen