Novel factor V C2-domain mutation (R2074H) in two families with factor V deficiency and bleeding.
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Schrijver I, Houissa-Kastally R, Jones CD, Garcia KC, Zehnder JL
Novel factor V C2-domain mutation (R2074H) in two families with factor V deficiency and bleeding.
Thromb Haemost. 2002 Feb;87(2):294-9.
- PubMed ID
- 11858490 [ View in PubMed]
- Abstract
The molecular basis of Factor V deficiency has been defined in few patients only. We report a homozygous nucleotide change (G6395A) in two Tunisian probands with Factor V deficiency and bleeding episodes. This substitution results in the replacement of an arginine (R) by a histidine (H) in amino acid position 2074, located in the Factor V C2-domain. Mutations in this protein domain have not previously been described. Several lines of evidence support that this sequence variant is indeed disease causing: 1) Crystal structures of Factor V and molecular C2-domain modeling studies of H2074 suggest that the conserved R2074 is required for correct folding; 2) Structure-function studies of selective Factor V mutants (R2074A) demonstrate the importance of R2074 for structural stability of the Factor V C2-domain and for cofactor activity (1); 3) In Factor VIII, point mutations in codon 2209, which corresponds to position 2074 in Factor V, cause hemophilia A.