Fibrinogen Baltimore I: polymerization defect associated with a gamma 292Gly----Val (GGC----GTC) mutation.
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.
Bantia
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Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Mane
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Bell
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Dang
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D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D001778:Blood Coagulation Disorders / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D003062:Codon; D005260:Female; D015241:Fibrinogens, Abnormal / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005344:Fibrinopeptide A / Q000378:metabolism; D005345:Fibrinopeptide B / Q000378:metabolism; D005998:Glycine / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011108:Polymers; D012697:Serine Endopeptidases / Q000378:metabolism; D014633:Valine / Q000235:genetics*
D003062:Codon; D015241:Fibrinogens, Abnormal; D011108:Polymers; C066651:fibrinogen Baltimore I; D005344:Fibrinopeptide A; D005345:Fibrinopeptide B; D012697:Serine Endopeptidases; C036813:lysyl endopeptidase; D014633:Valine; D005998:Glycine