A 28-year-old South-Asian woman has mild hemolytic anemia with elliptocytes, osmotic fragility slightly elevated, and a spectrin dimer self-association defect on gel electrophoresis. The molecular basis of hereditary elliptocytosis in most cases involves:
- A Mutations in alpha- or beta-spectrin disrupting the head-to-head spectrin tetramer formation ✓
- B Ankyrin gene mutations preventing spectrin attachment to band 3
- C Protein 4.2 mutations abolishing interaction with glycophorin A
- D Glucose-6-phosphate dehydrogenase deficiency reducing NADPH and allowing oxidative hemolysis
Correct answer: A. Mutations in alpha- or beta-spectrin disrupting the head-to-head spectrin tetramer formation
Explanation
The majority of hereditary elliptocytosis is caused by mutations in alpha-spectrin (SPTA1) or beta-spectrin (SPTB) affecting the N-terminal region of alpha-spectrin or the C-terminal region of beta-spectrin — the head contact site. Normal spectrin exists as alpha-beta heterodimers that associate head-to-head to form tetramers; defective tetramer formation destabilizes the membrane skeletal lattice, resulting in the elliptocyte shape. Ankyrin mutations cause hereditary spherocytosis.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.