A novel fibrinogen variant--Praha I: hypofibrinogenemia associated with gamma Gly351Ser substitution.
OBJECTIVE
A 25-yr-old man from Prague had abnormal bleeding after several surgical operations with low fibrinogen level and hypofibrinogenemia was suspected.


METHODS
The patient, 25 yr-old male had a low fibrinogen concentration as determined by the thrombin time and immunoturbidimetrical method. His 48-yr-old mother presented with normal coagulation tests, normal fibrinogen level and reported no history of bleeding. To identify the genetic mutation responsible for this hypofibrinogen, genomic DNA extracted from the blood was analyzed. Fibrin polymerization measurement, kinetics of fibrinopeptide release, fibrinogen clottability measurement, mass spectroscopy, and scanning electron microscopy were performed.


RESULTS
DNA sequencing showed heterogeneous fibrinogen gammaG351S mutation in the propositus. The mutant chain was found not to be expressed to the circulation by matrix-assisted laser desorption/ionization time of flight mass spectrometry. Scanning electron micrographs of the patient's fibrin clot as well as kinetics of fibrinopeptide release and fibrin polymerization were found to be normal.


CONCLUSIONS
A case of hypofibrinogenemia gammaG351S was found by routine coagulation testing and was genetically identified.
Kotlín
Roman
R
Institute of Hematology and Blood Transfusion, Praha, Czech Republic. kotlinr@uhkt.cz
Chytilová
Martina
M
Suttnar
Jirí
J
Salaj
Peter
P
Riedel
Tomás
T
Santrůcek
Jirí
J
Klener
Pavel
P
Dyr
Jan Evangelista
JE
D000328:Adult; D000595:Amino Acid Sequence; D001769:Blood; D005260:Female; D005340:Fibrinogen / Q000235:genetics* / Q000378:metabolism; D005998:Glycine / Q000235:genetics*; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D008969:Molecular Sequence Data; D012694:Serine / Q000235:genetics*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D012694:Serine; D005340:Fibrinogen; D005998:Glycine