Pathology Which of the following is the primary defect which leads to sickle cell anemia? A A nonsense mutation in the b-chain of HbA B An abnormality in porphyrin pa of hemoglobin C Replacement of glutamate by valine in b-chain of HbA D Substitution of valine by glutamate in the a-chain of HbA 💡 Explanation Which of the following is the primary defect which leads to sickle cell anemia? ✓ Correct Answer: C. Replacement of glutamate by valine in b-chain of HbA