Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Thrombosis and haemostasis, 2002-02, Vol.87 (2), p.294-299

Ort / Verlag

Germany

Erscheinungsjahr

2002

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.