Factor V Leiden

Factor V Leiden-  Hereditary Hypercoagulability

• Hypercoagulability: excessive blood clot formation
• Factor V Leiden: a mutation in Factor V protein
• Factor V is pro-coagulation protein
• When activated Factor V acts as a co-factor in activation of protombin to thrombin by factor Xa 
• Factor V is inactivated by activated protein C
• Type of mutation: missense mutation  G->A [ arginine -> glutamine]
• this mutation disable inactivation of Factor V by protein C
• this leads to excessive fibrin clots
• Diagnosis: PCR-RFLP (PCR of fragment gene followed with restriction of the product)
• Normal: Factor V gene has two restriction site by MnlI

                             ____67____|___37___|______163______

• three fragments are produced (163, 67, 37 bp)
• Mutant: Factor V gene has one restriction site by MnlI (the mutation destroys the second restriction site for MnlI endonuclease enzyme)
• two fragments are produced (200, 67 bp)

                           _____67____|_________200____________

• The fragments then run on a gel