Leiden mutation is
**Core Concept**
The Leiden mutation is a genetic variation in the factor V gene, leading to an increased risk of venous thromboembolism. It results from a point mutation at position 1691 in the factor V gene, leading to the substitution of arginine with glutamine at position 506 (R506Q).
**Why the Correct Answer is Right**
This mutation renders the factor V protein resistant to inactivation by activated protein C (APC), allowing it to remain active longer and contribute to thrombosis. APC normally inactivates factor Va by cleaving it at specific sites, but the Leiden mutation prevents this inactivation, leading to a hypercoagulable state. The R506Q mutation affects the cleavage site of factor Va and makes it less accessible to APC.
**Why Each Wrong Option is Incorrect**
* **Option A:** This option is not relevant to the Leiden mutation. Factor VII is a different coagulation factor, and its deficiency or mutation is associated with bleeding disorders, not thrombosis.
* **Option B:** This option is incorrect because the Leiden mutation does not involve a deficiency of protein C, but rather a mutation in factor V that makes it resistant to protein C's inactivation.
* **Option C:** This option is not correct because the Leiden mutation is not associated with a deficiency of antithrombin, which is a different anticoagulant protein.
**Clinical Pearl / High-Yield Fact**
The Leiden mutation is a common cause of inherited thrombophilia, and patients with this mutation should be screened for other risk factors of venous thromboembolism, such as immobilization, surgery, or cancer.
**Correct Answer: D. Factor V mutation leading to resistance to activated protein C.**