Characterization of fibrinogen New York 1. A dysfunctional fibrinogen with a deletion of B beta(9-72) corresponding exactly to exon 2 of the gene.
Fibrinogen New York 1 (NY-1) was identified in a family with a thrombotic tendency. Studies on fibrinogen NY-1 and the fibrinogen from her brother, designated NY-1a, showed that both have abnormal thrombin-nonclottable fibrinogen (50% of the total fibrinogen in NY-1 and 35-40% in NY-1a) and that the trait is heterozygous and autosomal codominant. The abnormal fibrinogen polymerizes in the presence of calcium and can be further cross-linked by Factor XIIIa. The release rates of fibrinopeptides A and B by thrombin from both (NY-1 and NY-1a) were slower than those from normal fibrinogen. Two mol of fibrinopeptide A but only 0.6-1.0 (NY-1) or 1.0-1.3 (NY-1a) mol of fibrinopeptide B were released per mol of fibrinogen. Additionally, only 1.0 (NY-1) or 1.3 (NY-1a) mol of the B beta(1-42) peptide were released by plasmin/mol. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the reduced fibrinogen revealed two protein bands in the B beta-chain region (Mr = 54,000 as compared with 57,300 for the normal). When NY-1a fibrinogen was treated with CNBr, two sizes of the NH2-terminal disulfide knot were obtained (Mr = 59,000 and 49,000). The Mr = 49,000 component is consistent with an abnormal NH2-terminal disulfide knot with two defective NH2-terminal B beta-chains. Amino acid sequence analyses demonstrated that the abnormal B beta-chain is the result of a deletion in the sequence from residues 9 to 72. This deletion corresponds exactly to exon 2 of the gene. Since this family has a thrombotic tendency, the defect in the fibrinogen may be important in the pathogenesis of thrombosis in this family.
Liu
C Y
CY
Koehn
J A
JA
Morgan
F J
FJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D003488:Cyanogen Bromide / Q000494:pharmacology; D004247:DNA / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005340:Fibrinogen / Q000032:analysis / Q000235:genetics*; D015241:Fibrinogens, Abnormal; D005341:Fibrinolysin / Q000378:metabolism; D005344:Fibrinopeptide A / Q000378:metabolism; D005345:Fibrinopeptide B / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D010375:Pedigree; D013927:Thrombosis / Q000235:genetics
D015241:Fibrinogens, Abnormal; C044790:fibrinogen New York 1; D005344:Fibrinopeptide A; D005345:Fibrinopeptide B; D005340:Fibrinogen; D004247:DNA; D005341:Fibrinolysin; D003488:Cyanogen Bromide