A novel fibrinogen variant (fibrinogen Seoul II; AalphaGln328Pro) characterized by impaired fibrin alpha-chain cross-linking.
We report a novel fibrinogen variant (fibrinogen Seoul II), which has a heterozygous point mutation from CAA to CCA leading to AalphaGln328Pro. The mutation site is among several glutamine residues that serve as alpha-chain cross-linking 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 to the emergency room due to recurrence of the disease, where he expired under treatment with tissue plasminogen activator (t-PA). Fibrin polymerization curves, made using purified fibrinogen from the patient's relatives, 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 Aalpha328 plays a pivotal role in alpha-chain cross-linking.
Park
Rojin
R
Department of Laboratory Medicine, Yongdong Severance Hospital, 146-92 Dogok-Dong, Kangnam-Gu, Seoul 135-720, Republic of Korea.
Doh
Hyun-Ju
HJ
An
Seong-Soo A
SS
Choi
Jong-Rak
JR
Chung
Kwang-Hoe
KH
Song
Kyung-Soon
KS
D000328:Adult; D000347:Afibrinogenemia / Q000097:blood / Q000235:genetics; D000368:Aged; D019943:Amino Acid Substitution; D001665:Binding Sites; D025861:Blood Coagulation Disorders, Inherited / Q000097:blood / Q000235:genetics; D002648:Child; D003432:Cross-Linking Reagents; D026122:Factor XIIIa / Q000378:metabolism; D005260:Female; D015241:Fibrinogens, Abnormal / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D046912:Multiprotein Complexes; D017354:Point Mutation; D010959:Tissue Plasminogen Activator / Q000009:adverse effects
D003432:Cross-Linking Reagents; D015241:Fibrinogens, Abnormal; D046912:Multiprotein Complexes; D026122:Factor XIIIa; D010959:Tissue Plasminogen Activator