A novel fibrinogen variant--Liberec: dysfibrinogenaemia associated with gamma Tyr262Cys substitution.
OBJECTIVE
A 22-yr-old woman had abnormal preoperative coagulation test results and congenital dysfibrinogenaemia was suspected.


METHODS
The patient from Liberec (Czech Republic) had a low fibrinogen plasma level as determined by Clauss method, normal fibrinogen level as determined by immunoturbidimetrical method, and prolonged thrombin time. To identify the genetic mutation responsible for this dysfibrinogen, genomic DNA extracted from the blood was analysed. Fibrin polymerisation measurement, kinetics of fibrinopeptide release, fibrinogen clottability measurement and scanning electron microscopy were performed.


RESULTS
DNA sequencing showed the heterozygous fibrinogen gamma Y262C mutation. Kinetics of fibrinopeptide release was normal, however fibrin polymerisation was impaired. Fibrinogen clottability measurement showed that only about 45% molecules of fibrinogen are involved in the clot formation. Scanning electron microscopy revealed thicker fibres, which were significantly different from the normal control.


CONCLUSIONS
A case of dysfibrinogenaemia, found by routine coagulation testing, was genetically identified as a novel fibrinogen variant (gamma Y262C) that has been named Liberec.
Kotlín
Roman
R
Institute of Haematology and Blood Transfusion, Praha 2, Czech Republic. kotlinr@uhkt.cz
Sobotková
Alzbeta
A
Suttnar
Jirí
J
Salaj
Peter
P
Walterová
Lenka
L
Riedel
Tomás
T
Reicheltová
Zuzana
Z
Dyr
Jan Evangelista
JE
D000328:Adult; D000347:Afibrinogenemia / Q000235:genetics*; D001777:Blood Coagulation / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D015241:Fibrinogens, Abnormal / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense
D015241:Fibrinogens, Abnormal