In hereditary spherocytosis (HS), the red cell membrane defect most commonly involves mutations in which protein?

• A Glycophorin A — sialoglycoprotein carrying MN blood group antigens
• B Ankyrin (ANK1) — the most common cause, linking spectrin to band 3 ✓
• C Glucose-6-phosphate dehydrogenase (G6PD) — enzyme for oxidative stress protection
• D Haemoglobin beta chain — causing beta-thalassaemia major

Explanation

In hereditary spherocytosis, the most frequent molecular defect is in ankyrin (ANK1, ~65% of cases), which bridges the spectrin-actin cytoskeletal network to the lipid bilayer via band 3. Mutations in spectrin (alpha or beta), band 3, and protein 4.2 account for the remaining cases. Vertical loss of lipid bilayer support causes membrane fragmentation into spheres, which are trapped and haemolysed in the spleen.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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