Novel factor V C2-domain mutation (R2074H) in two families with factor V deficiency and bleeding.

I Schrijver, R Houissa-Kastally, C D Jones, K C Garcia, J L Zehnder

Journal: Thrombosis and haemostasis 2002;87(2):294-9

PMID: 11858490

Full Text on Ovid Technologies, Inc. View on 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.

Address: Department of Pathology, Stanford University School of Medicine, CA 94305, USA.

Link outs

Free resources

Miscellaneous:

https://assays.cancer.gov/non-CPTAC-1104

Molecular Biology Databases:

https://glygen.org/publication/PubMed/11858490/

Subscription / membership required

Full Text Sources:

http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linko...

MeSH Terms: Amino Acid Sequence, Amino Acid Substitution, Consanguinity, Diseases in Twins, Factor V, Factor V Deficiency, Female, Humans, Male, Models, Molecular, Molecular Sequence Data, Mutation, Missense, Pedigree, Point Mutation, Protein Conformation, Protein Structure, Tertiary, Sequence Alignment, Tunisia