title: Coexisting congenital dysfibrinogenemia with a novel mutation in fibrinogen γ chain (γ322 Phe→Ile, Fibrinogen Beijing) and haemophilia B in a family.
abstract: BACKGROUND
  Both congenital dysfibrinogenemia and haemophilia B (HB) are rare coagulopathies caused by mutations within the fibrinogen and F9 genes respectively.
  
  
  OBJECTIVE
  To investigate the pathogenesis of combined dysfibrinogenemia with HB in a family.
  
  
  METHODS
  Coagulation assays, factor IX (FIX) activity (one-stage method), fibrinogen activity (Clauss method), antigen (immunoturbidimetry), fibrinogen polymerization and fibrinolysis velocity were measured. The sequences of fibrinogen genes and F9 were amplified by PCR and analysed by sequencing.
  
  
  RESULTS
  The proband, a 16-year-old boy with HB (FIX 2 IU dL(-1) ), also had persistently low Clauss fibrinogen level (0.64-0.65 g L(-1) ) with normal antigen level (2.23 g L(-1) ). The mother had a FIX 45 IU dL(-1) and similarly discrepant low Clauss fibrinogen (0.79 g L(-1) ) to antigen levels (2.23 g L(-1) ). Thrombin time for both were either slightly prolonged or at boundary value. Genetic analysis of the proband and the mother identified similar mutations in the FGG gene (heterozygous c.1042T>A resulting in p.Phe348Ile or γPhe322Ile in the mature protein) and in the F9 gene (c.1243del p.His415Metfs*11 and c.1245T>A p.His415Gln). The father had no fibrinogen or F9 gene mutations. Plasma fibrinogen polymerization was delayed, but fibrinolysis velocity was normal in the proband and his mother.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report of a family with combined novel dysfibrinogen (Fibrinogen Beijing) and HB with bleeding manifestations.
authors.affiliation: Department of Hematology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Hua
authors.affiliation: Department of Hematology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.
authors.forename: K
authors.initials: K
authors.lastname: Li
authors.affiliation: Foothills Medical Centre, University of Calgary, Calgary, AB, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.affiliation: Foothills Medical Centre, University of Calgary, Calgary, AB, Canada.
authors.forename: M-C
authors.initials: MC
authors.lastname: Poon
authors.affiliation: Department of Hematology, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000347:Afibrinogenemia / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D001780:Blood Coagulation Tests; D004252:DNA Mutational Analysis; D005260:Female; D005340:Fibrinogen / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005342:Fibrinolysis; D002836:Hemophilia B / Q000150:complications*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary
chemical_list: C427756:P2-C protein, fibrinogen; D010446:Peptide Fragments; D005340:Fibrinogen
keywords: F9; FGG; dysfibrinogenemia; haemophilia B; mutation