Submitted November 10, 2005
Accepted May 9, 2006
A Novel Fibrinogen Variant (Fibrinogen Seoul II;
A
Gln328Pro) Characterized by Impaired Fibrin
-chain Cross-linking
Rojin Park, Hyun-Ju Doh, Seong-Soo A An, Jong-Rak Choi, Kwang-Hoe Chung, and Kyung-Soon Song*
Department of Laboratory Medicine, Soon Chun Hyang University Hospital
BioBud Research Institute
PeopleBio Research Institute
Yonsei University College of Medicine
Department of Laboratory Medicine, Yonsei University College of Medicine
* Corresponding author; email: kssong{at}yumc.yonsei.ac.kr.
We report a novel fibrinogen variant (Fibrinogen Seoul
II), which has a heterozygous point mutation from CAA to
CCA leading to A
Gln328Pro. The mutation site is
among several glutamine residues that serve as
chain crosslinking acceptor sites. Fibrinogen Seoul II
was found in a 51 year-old male patient and his family
in Seoul, Korea. The patient was diagnosed with
myocardial infarction at age 43. Eight years later he
was admitted due to recurrence of the disease to the
emergency room, where he expired under treatment with
tissue plasminogen activator (t-PA). Fibrin polymerization
curves, made using purified fibrinogen from the patient¡ s
relatives with the same molecular defect, showed a
decreased final turbidity, suggesting Seoul II fibrin
clots are composed of thinner fibers. This supposition was
verified using scanning electron microscopy. Alpha polymer
formation by the mutant fibrinogen upon thrombin treatment
in the presence of factor XIII and calcium was distinctly
impaired. This result confirms that the residue
A328Pro plays a pivotal role in chain
crosslinking.
