Polymerization defect of fibrinogen Baltimore III due to a gamma Asn308-
---Ile mutation
S Bantia, WR Bell and CV Dang
Department of Medicine, Johns Hopkins University School of Medicine,
Baltimore, MD.
Fibrinogen Baltimore III, a congenital abnormal fibrinogen with impaired
fibrin monomer polymerization, displays a normal gamma-chain and a
gamma-variant that has an apparently lower relative molecular weight (mol
wt) than normal on sodium dodecyl sulfate-polyacrylamide gel
electrophoresis (SDS-PAGE). Reverse phase high-performance liquid
chromatography (HPLC) analysis of the lysyl endopeptidase digest of the
purified gamma-chains of fibrinogen Baltimore III revealed the presence of
a peptide that is not found in the digest of the normal fibrinogen
gamma-chain. Amino acid sequence analysis of this peptide indicated that
the gamma-chain residue 308, asparagine, is replaced by isoleucine.
Concanavalin A bound both normal and variant gamma-chains of fibrinogen
Baltimore III, indicating that the carbohydrate moiety is not altered and
is not responsible for the increase in electrophoretic mobility of the
Baltimore III gamma-chain. This study suggests that the integrity of gamma
Asn308 is critical for fibrin monomer polymerization, since alteration to
either a basic (fibrinogen Kyoto I, Asn----Lys) or hydrophobic (Asn----Ile)
residue results in significantly delayed polymerization of fibrinogen to
fibrin.
Volume 75,
Issue 8,
pp. 1659-1663,
04/15/1990
Copyright © 1990 by The American Society of Hematology
