title: Two novel mutations in the fibrinogen γ nodule.
abstract: BACKGROUND
  Congenital dysfibrinogenemia and hypofibrinogenemia are rare diseases characterized by inherited abnormality in the fibrinogen molecule, resulting in functional defects (dysfibrinogenemia) or low fibrinogen plasma levels (hypofibrinogenemia).
  
  
  METHODS
  We have described two abnormal fibrinogens - fibrinogen Hranice (γ Phe204Val) and Praha IV (γ Ser313Gly). The carrier of the Hranice mutation was a 40-year-old female with low fibrinogen levels. The carrier of the Praha IV mutation was a 42-year-old man with a history of idiopathic thrombosis, low functional fibrinogen levels, and a prolonged thrombin time.
  
  
  RESULTS
  Fibrin polymerization kinetics measurement was normal in both cases (after the addition of either thrombin or reptilase), as well as was fibrinolysis. Scanning electron microscopy and confocal microscopy revealed significantly wider fibers in both cases, when compared with fibers prepared from healthy control samples. Although both cases are situated in the γ-nodule, they manifested differently. While the γ Ser313Gly mutation manifested as dysfibrinogenemia with a thrombotic background, the γ Phe204Val mutation manifested as hypofibrinogenemia without clinical symptoms. The mutation sites of both fibrinogens are in highly conserved regions of the fibrinogen γ chains. γ Ser313 is situated in a class 16:18 β hairpin and is involved in hydrogen bonding with γ Asp320. γ Phe204 is situated in an inverse γ turn and may be involved in π-π interactions.
  
  
  CONCLUSIONS
  Both mutations cause conformational changes in fibrinogen, which lead either to impaired fibrinogen assembly (fibrinogen Hranice) or abnormal fibrinogen function (fibrinogen Praha IV).
authors: Institute of Hematology and Blood Transfusion, U nemocnice 1, 128 20 Prague 2, Czech Republic. Electronic address: kotlinr@uhkt.cz.
authors: Roman
authors: R
authors: Kotlín
authors: Institute of Hematology and Blood Transfusion, U nemocnice 1, 128 20 Prague 2, Czech Republic.
authors: Ondřej
authors: O
authors: Pastva
authors: Institute of Hematology and Blood Transfusion, U nemocnice 1, 128 20 Prague 2, Czech Republic.
authors: Jana
authors: J
authors: Stikarová
authors: Institute of Hematology and Blood Transfusion, U nemocnice 1, 128 20 Prague 2, Czech Republic.
authors: Alžběta
authors: A
authors: Hlaváčková
authors: Institute of Hematology and Blood Transfusion, U nemocnice 1, 128 20 Prague 2, Czech Republic.
authors: Jiří
authors: J
authors: Suttnar
authors: Institute of Hematology and Blood Transfusion, U nemocnice 1, 128 20 Prague 2, Czech Republic.
authors: Leona
authors: L
authors: Chrastinová
authors: Institute of Hematology and Blood Transfusion, U nemocnice 1, 128 20 Prague 2, Czech Republic; Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, v.v.i., Heyrovského náměstí 2, 162 06 Prague 6, Czech Republic.
authors: Tomáš
authors: T
authors: Riedel
authors: Institute of Hematology and Blood Transfusion, U nemocnice 1, 128 20 Prague 2, Czech Republic.
authors: Peter
authors: P
authors: Salaj
authors: Institute of Hematology and Blood Transfusion, U nemocnice 1, 128 20 Prague 2, Czech Republic.
authors: Jan E
authors: JE
authors: Dyr
mesh_terms: D000328:Adult; D000347:Afibrinogenemia / Q000097:blood / Q000151:congenital* / Q000235:genetics / Q000378:metabolism; D005260:Female; D005337:Fibrin / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D005340:Fibrinogen / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D015241:Fibrinogens, Abnormal / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D005342:Fibrinolysis; D006801:Humans; D008297:Male; D017354:Point Mutation
chemical_list: D015241:Fibrinogens, Abnormal; C027539:fibrinopeptides gamma; D005337:Fibrin; D005340:Fibrinogen
keywords: Abnormal fibrinogens; Coagulation; Fibrinogen; Hereditary coagulation disorders; Thrombosis