In hereditary spherocytosis (HS), the primary molecular defect most commonly affects which red cell membrane protein pair?
- A Spectrin-ankyrin interaction (ankyrin or spectrin mutations most common) ✓
- B Band 3-protein 4.2 complex
- C Glycophorin C
- D Protein 4.1 — glycophorin A interaction
Correct answer: A. Spectrin-ankyrin interaction (ankyrin or spectrin mutations most common)
Explanation
Hereditary spherocytosis most commonly results from mutations in ANK1 (ankyrin, ~40-65%) or SPTB/SPTA1 (spectrin, ~15-30%), disrupting the spectrin-ankyrin-band 3 vertical linkage between the lipid bilayer and the submembrane cytoskeleton. Loss of membrane lipid bilayer portions causes the biconcave disk to become a sphere with reduced surface-to-volume ratio, increased osmotic fragility, and splenic sequestration. Band 3-protein 4.2 mutations cause a milder subtype of HS. Protein 4.1 mutations cause hereditary elliptocytosis.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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