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Thromb Haemost 1998; 79(06): 1136-1143
DOI: 10.1055/s-0037-1615030
Rapid Communication
Schattauer GmbH

Characterization of a Factor VII Molecule Carrying a Mutation in the Second Epidermal Growth Factor-like Domain

Anita Kavlie
1   From the Biotechnology Centre of Oslo, University of Oslo
,
Lars Örning
2   Nycomed Pharma A/S, Oslo, Norway
,
Anne Grindflek
1   From the Biotechnology Centre of Oslo, University of Oslo
,
Helge Stormorken
3   Research Institute for Internal Medicine, University of Oslo, Oslo, Norway
,
Hans Prydz
1   From the Biotechnology Centre of Oslo, University of Oslo
› Author Affiliations
Further Information

Publication History

Received 18 July 1997

Accepted after resubmission 04 February 1998

Publication Date:
07 December 2017 (online)

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Summary

A missense mutation at codon 100 in the second epidermal growth factor-like domain, resulting in Gln100→Arg, was detected in 19 out of 21 available severely factor VII (FVII) deficient patients in Norway. Seventeen patients were homozygous, and the two remaining were compound heterozygotes. In the homozygous patients, FVII antigen was measured to 10-28%, and activity to 0.6-6.5% of that in normal pooled plasma. Recombinant FVII containing the mutation was expressed transiently in CHO cells to a mean antigen level of 57% of the wild type FVII protein, and with a specific activity of 6% of wild type. The mutant protein had a 14-fold reduction in affinity for tissue factor (TF), whereas binding of FX seemed unaffected. In line with the experimental data, molecular modelling of the mutation based on the coordinates of the tissue factor/FVIIa complex showed that substituting arginine for glutamine disrupts the interface between the catalytic and second epidermal growth factor-like domains.

 

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