Fibrinogen Baltimore I: polymerization defect associated with a gamma
292Gly----Val (GGC----GTC) mutation
S Bantia, SM Mane, WR Bell and CV Dang
Department of Medicine, Johns Hopkins University School of Medicine,
Baltimore, MD 21205.
Fibrinogen Baltimore I is one of the very first congenital abnormal
fibrinogens reported over several decades ago; however, the molecular
defect of this dysfibrinogen has eluded identification. In fact, several
reports misidentified the functional defect of Baltimore I, which has
impaired fibrin monomer polymerization. Reversed-phase high- performance
liquid chromatography analysis of lysyl endopeptidase digest of the
purified Baltimore I gamma-chain showed an abnormal peptide not found in
the co-existing normal gamma-chain of this heterozygote. Amino acid
sequencing of this peptide indicated that gamma-chain Gly292 is replaced by
valine. This observation was confirmed, and the genetic defect was
determined by direct nucleotide sequencing of a polymerase chain reaction
product containing codon gamma 292, which is mutated: GGC----GTC. The
molecular defect of Fibrinogen Baltimore I lies in a region of the
gamma-chain required for fibrin polymerization, suggesting that the
integrity of gamma Gly292 is critical for fibrin assembly.
Volume 76,
Issue 11,
pp. 2279-2283,
12/01/1990
Copyright © 1990 by The American Society of Hematology
