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Novel factor VC2-domain mutation (R2074H) in two families with factor V deficiency and bleeding THROMBOSIS AND HAEMOSTASIS Schrijver, I., Houissa-Kastally, R., Jones, C. D., Garcia, K. C., Zehnder, J. L. 2002; 87 (2): 294-299

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.

View details for Web of Science ID 000173869300020

View details for PubMedID 11858490