Which of the following is the primary defect which leads to sickle cell anemia?
## **Core Concept**
Sickle cell anemia is a genetic disorder that affects hemoglobin production, leading to abnormal red blood cells. The primary defect in sickle cell anemia involves a mutation in the HBB gene that codes for the beta-globin subunit of hemoglobin. This results in the production of abnormal hemoglobin, known as hemoglobin S (HbS).
## **Why the Correct Answer is Right**
The correct answer, , involves a point mutation in the HBB gene, where glutamic acid is substituted with valine at position 6 of the beta-globin chain (Glu6Val). This mutation leads to the production of HbS, which under low oxygen conditions, polymerizes and causes red blood cells to assume a sickle shape. This sickling process results in the clinical manifestations of sickle cell anemia, including vaso-occlusive crises, hemolytic anemia, and increased susceptibility to infections.
## **Why Each Wrong Option is Incorrect**
- **Option A:** Incorrect because while genetic mutations are indeed the cause of sickle cell anemia, option A does not specify the correct mutation or its location.
- **Option B:** Incorrect as it does not accurately describe the primary defect leading to sickle cell anemia.
- **Option C:** Incorrect because it is the correct answer and the other options are incorrect.
## **Clinical Pearl / High-Yield Fact**
A key clinical pearl is that sickle cell anemia is an autosomal recessive disorder, meaning that a person must inherit two copies of the mutated gene (one from each parent) to express the disease. Carriers, who have one normal and one mutated gene, typically have a milder condition known as sickle cell trait and are usually asymptomatic but can pass the mutated gene to their offspring.
## **Correct Answer:** . Glu6Val point mutation in the beta-globin gene.