Sickle cell anemia is the clinical manifestation of homozygous gene to an abnormal haemoglobin molecule. The event responsible for the mutation in the b chain is:
**Question:** Sickle cell anemia is the clinical manifestation of homozygous gene to an abnormal haemoglobin molecule. The event responsible for the mutation in the b chain is:
A. Glu6Val substitution
B. Glu6Lys substitution
C. Pro6Val substitution
D. Gly10Val substitution
**Correct Answer:** .
**Core Concept:** Sickle cell anemia is a hereditary blood disorder caused by mutations in the HBB gene, which codes for the beta-globin subunit of hemoglobin (Hb). The most common mutation is the A allele, where the amino acid valine replaces glutamic acid at position 6 (Glu6Val substitution). This results in an abnormal hemoglobin molecule, hemoglobin S (HbS), which polymerizes under low oxygen tension, leading to sickle-shaped red blood cells.
**Why the Correct Answer is Right:** The correct answer is A (Glu6Val substitution) because it describes the specific mutation that leads to the formation of hemoglobin S (HbS), the abnormal hemoglobin responsible for the pathophysiology of sickle cell anemia. The other options represent different types of mutations that do not result in the formation of HbS, hence they are incorrect.
**Why Each Wrong Option is Incorrect:**
- Option B: Glu6Lys substitution (Glu6Lys) is an incorrect mutation since lysine does not polymerize under low oxygen tension, unlike valine.
- Option C: Pro6Val substitution (Pro6Val) is an incorrect mutation because proline does not polymerize under low oxygen tension, unlike valine.
- Option D: Gly10Val substitution (Gly10Val) is an incorrect mutation because the mutation occurs at a different position on the beta-globin chain, not related to HbS formation.
**Clinical Pearl:** Understanding the molecular basis of sickle cell anemia is crucial for diagnosing and managing patients with this condition. Knowledge of the Glu6Val substitution allows healthcare professionals to recognize the disease and provide appropriate counseling and management strategies for affected individuals and their families.
**Correct Answer:** Glu6Val substitution (A)