On peripheral smear of a patient with hereditary spherocytosis, the spherocytes lack central pallor and have increased MCHC. The underlying molecular defect most commonly involves which cytoskeletal protein?

• A Ankyrin (band 2.1) ✓
• B Hemoglobin beta-chain
• C Glycophorin A
• D Band 3 protein alone in all cases

Explanation

Ankyrin deficiency (encoded by ANK1 on chromosome 8) is the most common molecular defect in hereditary spherocytosis (~50% of cases), followed by spectrin (alpha and beta) and band 3 deficiencies. Loss of ankyrin disrupts the vertical linkage between the lipid bilayer and the underlying spectrin-actin cytoskeleton, causing membrane vesiculation and spherocyte formation. Hemoglobin beta-chain mutations cause thalassemia or HbS, not HS. Glycophorin A deficiency causes En(a−) blood group, not HS.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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