Genetic and Pediatric Diseases · USMLE Step 1

Sickle cell disease (SCD) is caused by a mutation in which gene product, and what is the primary pathologic change in red blood cells?

  1. CFTR channel defect causing thick mucus
  2. Hemoglobin β-chain defect causing rigid sickled cells
  3. Hexosaminidase A deficiency with neuronal lipid buildup
  4. Fibrillin-1 defect causing weak connective tissue
Show answer and explanation

Correct answer: Hemoglobin β-chain defect causing rigid sickled cells

SCD arises from a point mutation in the β-globin gene, causing abnormal hemoglobin (HbS). Under low oxygen tension, red blood cells distort into sickle shapes — rigid and prone to hemolysis and vaso-occlusion.

Difficulty: Medium Question 5 of 20

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