title: [Congenital hypofibrinogenemia associated with a novel mutation in FGG gene].
abstract: OBJECTIVE
  To identify the genetic mutation underlying congenital hypofibrinogenamia in a Chinese pedigree.
  
  
  METHODS
  Standard coagulation tests including the prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), plasminogen activity (PLG:A), D-Dimer (DD) and fibrin degradation products (FDP) were tested with fresh plasma using a STA-R analyzer. The activity of fibrinogen (Fg:C) and fibrinogen antigen (Fg:Ag) were measured respectively with the Clauss method and immunoturbidimetry. All exons and exon-intron boundaries of the fibrinogen Aα-, Bβ-, and γ-chain genes (FGA, FGB and FGG) were amplified by PCR followed by direct sequencing. Suspected mutation was confirmed by reverse sequencing and analyzed with a Swiss-PdbViewer.
  
  
  RESULTS
  The PT level in the proband was normal, while the APTT and TT were slightly prolonged. The functional and antigen fibrinogen levels were both significantly reduced (0.91 g/L and 0.95 g/L, respectively). Similar abnormalities were also found in her father, elder sister, son and niece. The coagulant parameters of her mother were all within the normal range. Genetic analysis has reveled a heterozygous A>C change at nucleotide 5864 in exon 7 of γ gene in the proband, predicting a novel Lys232Thr mutation. The proband's father, elder sister, son and niece were all carriers of the same mutation. Protein model analysis indicated that the Lys232Thr mutation did not disrupt the native network of hydrogen bonds, but has changed the mutual electrostatic forces, resulting in increased instability of the protein.
  
  
  CONCLUSIONS
  The heterozygous Lys232Thr mutation identified in the FGG gene probably underlies the hypofibrinogenemia in this pedigree.
authors.affiliation: Department of Clinical Laboratory, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R.China. wywms@126.com.
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Wang
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Ding
authors.forename: Xiuping
authors.initials: X
authors.lastname: Hao
authors.forename: Liqing
authors.initials: L
authors.lastname: Zhu
authors.forename: Lihong
authors.initials: L
authors.lastname: Yang
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Jin
authors.forename: Mingshan
authors.initials: M
authors.lastname: Wang
mesh_terms: D000328:Adult; D000347:Afibrinogenemia / Q000151:congenital* / Q000235:genetics; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D010446:Peptide Fragments / Q000235:genetics*; D055815:Young Adult
chemical_list: D010446:Peptide Fragments; C524059:fibrinogen gamma (151-411); D005340:Fibrinogen