Fibrinogen Bern I: substitution gamma 337 Asn-->Lys is responsible for
defective fibrin monomer polymerization
C Steinmann, P Reber, M Jungo, B Lammle, G Heinemann, B Wermuth and M Furlan
Central Hematology Laboratory, Inselspital, University of Bern,
Switzerland.
An inherited fibrinogen variant, fibrinogen Bern I, was isolated from
plasma of an asymptomatic woman. Routine coagulation studies showed
prolonged thrombin and reptilase clotting times. Fibrinogen concentration
was diminished when determined by a functional assay, but was normal by the
heat precipitation method. The release of fibrinopeptides A and B was not
delayed. Two-dimensional gel electrophoresis of mercaptolyzed fragments D
of fibrinogen, obtained by digestion with plasmin, showed an abnormal
electrophoretic mobility in the gamma-chain remnants of fragments D1 and D2
from fibrinogen Bern I, whereas conversion of D2 to D3 by plasmin resulted
in the loss of the abnormal charge, suggesting that the structural
abnormality in this variant is located in the region gamma 303 through 356.
The molecular defect in fibrinogen Bern I was identified by sequence
analysis of genomic DNA amplified by polymerase chain reaction and cloned
in M13mp19. The triplet AAC coding for asparagine at position gamma 337 was
found to be substituted by AAA coding for lysine. We conclude that the
substitution gamma 337 Asn-->Lys in fibrinogen Bern I is responsible for
defective polymerization of fibrin monomers and for impaired protection by
calcium against plasmic degradation.
Volume 82,
Issue 7,
pp. 2104-2108,
10/01/1993
Copyright © 1993 by The American Society of Hematology
