A new type of congenital dysfibrinogen, fibrinogen Bremen, with an A alpha Gly-17 to Val substitution associated with hemorrhagic diathesis and delayed wound healing.

Abstract

We have identified a new type of A alpha Gly-17 to Val substitution in a congenital dysfibrinogen, fibrinogen Bremen, derived from a 15-year-old boy having manifested easy bruising and delayed wound healing. The functional abnormality was characterized by altered fibrin monomer polymerization, which became evident by increasing the salt concentration and pH. A synthetic tetrapeptide with a sequence of the amino-terminal segment of normal fibrin alpha-chain, Gly-Pro-Arg-Val, substantially inhibited polymerization of both normal and the patient-derived fibrin monomers. A synthetic tetrapeptide with the Bremen type sequence of Val-Pro-Arg-Val inhibited polymerization of the patient's fibrin monomers partially at a peptide: fibrin monomer molar ratio of 4,000:1, and that of normal one at a much higher ratio of 10,000:1. Likewise, a synthetic peptide Ala-Pro-Arg-Val with a replacement of the Gly residue by another aliphatic amino acid Ala inhibited similarly the patient's fibrin monomer polymerization. Thus, the hypothetical two-pronged socket-like structure consisting of the alpha-amino group of the amino-terminal Gly and the guanidino group of an Arg at position 3 of the normal fibrin alpha-chain seems to be restored considerably in the mutant fibrin alpha-chain at low ionic strengths and pH's, despite the replacement of the amino-terminal Gly by another aliphatic amino acid Val.

• Authors: Y Wada, K Niwa, H Maekawa, S Asakura, T Sugo, M Nakanishi, G Auerswald, M Popp, M Matsuda
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 70 Issue 3 Pg. 397-403 (Sep 01 1993) ISSN: 0340-6245 [Print] Germany
• PMID: 8259537 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biopolymers
• Fibrinogens, Abnormal
• Peptide Fragments
• fibrinogen Bremen
• Valine
• Glycine

Topics

• Adolescent
• Amino Acid Sequence
• Biopolymers
• Fibrinogens, Abnormal (genetics, pharmacology)
• Glycine (genetics)
• Hemorrhagic Disorders (blood)
• Humans
• Male
• Molecular Sequence Data
• Mutation
• Peptide Fragments (genetics)
• Time Factors
• Valine (genetics)
• Wound Healing (physiology)