Fibrinogen Alès: a homozygous case of dysfibrinogenemia (gamma-Asp(330)--Val) characterized by a defective fibrin polymerization site 'a'
| Autor: | K C, Lounes, C, Soria, S S, Mirshahi, P, Desvignes, M, Mirshahi, O, Bertrand, P, Bonnet, J, Koopman, J, Soria |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adult
Male Fibrin Binding Sites Fibrinogens Abnormal Thrombin Time Homozygote Thrombin Thrombosis Coagulation Protein Disorders Blood Coagulation Disorders Afibrinogenemia Hemostatics Stroke Protein Subunits Amino Acid Substitution Fibrinolytic Agents Mutation Humans Thrombophilia Electrophoresis Polyacrylamide Gel Fibrinolysin Protein Binding |
| Zdroj: | Blood. 96(10) |
| ISSN: | 0006-4971 |
| Popis: | Congenital homozygous dysfibrinogenemia was diagnosed in a man with a history of 2 thrombotic strokes before age 30. His hemostatic profile was characterized by a dramatically prolonged plasma thrombin clotting time, and no clotting was observed with reptilase. Complete clotting of the abnormal fibrinogen occurred after a prolonged incubation of plasma with thrombin. The release of fibrinopeptides A and B by thrombin and of fibrinopeptide A by reptilase were both normal. Thrombin-induced fibrin polymerization was impaired, and no polymerization occurred with reptilase. The polymerization defect was characterized by a defective site "a," resulting in an absence of interaction between sites A and a, indicated by the lack of fragment D(1) (or fibrinogen) binding to normal fibrin monomers depleted in fibrinopeptide A only (Des-AA fm). By SDS-PAGE, the defect was detected on the gamma-chain and in its fragment D(1). The molecular defect determined by analysis of genomic DNA showed a single base change (A--T) in exon VIII of the gamma-chain. The resulting change in the amino acid structure is gamma 330 aspartic acid (GAT) --valine (GTT). It is concluded that the residue gamma-Asp(330) is essential for the normal functioning of the polymerization site a on the fibrinogen gamma-chain. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|