Prothrombin Greenville, Arg(517)-> Gln, identified in an individual heterozygous for dysprothrombinemia

作者：Henriksen RA^*; Dunham CK; Miller LD; Casey JT; Menke JB; Knupp CL; Usala SJ

来源：Blood, 1998, 91(6): 2026-2031.

A 64-year-old white male was referred for evaluation of prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT) obtained before elective surgery with initial PT and PTT results of 14.9 and 38.4 seconds, respectively, which corrected to normal in 1:1 mixes with normal plasma, Functional prothrombin assay indicated a level of 51% with thromboplastin as an activator. The prothrombin antigen was 102%. This discordance in the functional and immunologic prothrombin levels was evidence for dysprothrombinemia. Western blotting showed that thrombin was formed at a normal rate in diluted plasma consistent with a mutation within the thrombin portion of prothrombin. DNA was isolated from leukocytes and the thrombin exons were For exon 13, eight clones were sequenced with four clones showing a point mutation in the codon for Arg((517), which would result in substitution by Gin. Arg(517) is part of the Arg-Gly Asp(RGD) sequence in thrombin and contributes to an ion cluster with aspartic acid residues 552 and 554. Mutation at this residue most probably distorts the structure of the Naf binding site in thrombin. This is the first report indicating the critical role of Arg(517) in the normal physiological interaction of thrombin with fibrinogen. This dysprothrombin is designated Prothrombin Greenville.

• 出版日期1998-3-15