A 28-year-old woman presents for follow-up after a recent hospital admission for an unprovoked deep vein thrombosis in her right lower extremity. She has no significant past medical history, does not smoke, and does not take oral contraceptives. Her mother had a pulmonary embolism at age 42. Laboratory evaluation demonstrates that the addition of activated protein C (APC) to the patient's plasma fails to appropriately prolong the activated partial thromboplastin time (aPTT). Which of the following is the most likely molecular mechanism underlying this patient's condition?
- ADecreased hepatic synthesis of a vitamin K-dependent anticoagulant
- BAutoantibody production directed against phospholipid-binding proteins
- Point mutation leading to an amino acid substitution in a coagulation factorAnswer
- DGain-of-function mutation in the untranslated region of a coagulation gene
- ETrinucleotide repeat expansion in a non-coding gene region
Answer
Point mutation leading to an amino acid substitution in a coagulation factor
The correct answer accurately describes the molecular mechanism of Factor V Leiden. Factor V Leiden is the most common inherited thrombophilia and is caused by a missense point mutation (G1691A) in the F5 gene. This mutation leads to a single amino acid substitution (arginine replaced by glutamine at position 506) in the Factor V protein. This specific alteration eliminates the cleavage site for activated protein C, rendering the mutated Factor Va resistant to degradation and resulting in a prolonged procoagulant effect.
Step-by-Step Solution
Key Concept
Factor V Leiden is an inherited thrombophilia caused by a missense point mutation that leads to a single amino acid substitution in Factor V, rendering it resistant to degradation by activated protein C.