Factor V Leiden is caused due to a mutation that results in a substitution at position 506 glutamine to which of the following:
**Core Concept**
Factor V Leiden is a common genetic mutation in the coagulation cascade, specifically in the Factor V protein, where a single nucleotide substitution leads to resistance to inactivation by activated protein C (APC). This results in prolonged clotting time and increased risk of venous thromboembolism.
**Why the Correct Answer is Right**
The mutation involves a substitution of **glutamine (Q)** at position 506 to **arginine (R)** in the Factor V protein. This change occurs in the phospholipid-binding domain and disrupts the cleavage site for activated protein C. As a result, Factor V remains in its active form longer, promoting uncontrolled thrombin generation and hypercoagulability. The mutation is a point mutation in the *F5* gene, specifically a G→A transition.
**Why Each Wrong Option is Incorrect**
Option A: Alanine substitution does not occur in Factor V Leiden and would not confer resistance to APC inactivation.
Option C: Glycine substitution is not associated with this mutation and is not found in the natural variant.
Option D: Glutamine to glutamine is a silent mutation and does not alter protein function or structure.
**Clinical Pearl / High-Yield Fact**
Factor V Leiden is the most common inherited thrombophilic mutation, especially in individuals of European descent. It is a **gain-of-function** mutation that leads to **resistance to activated protein C**, resulting in a hypercoagulable state and increased risk of deep vein thrombosis (DVT) and pulmonary embolism.
✓ Correct Answer: B. Arginine