A renal biopsy from a child with nephrotic syndrome shows normal light microscopy, negative immunofluorescence, and effacement of podocyte foot processes on electron microscopy. The pathogenesis involves dysfunction of which podocyte protein most directly linked to the filtration slit diaphragm?
- A Alpha-actinin-4
- B CD2AP
- C Nephrin ✓
- D Podocin
Correct answer: C. Nephrin
Explanation
Minimal change disease involves loss of the normal charge barrier and slit diaphragm integrity; nephrin (encoded by NPHS1) is the major structural protein of the slit diaphragm forming a zipper-like scaffold between adjacent podocyte foot processes. Loss of nephrin function — whether through circulating permeability factors, antibodies, or mutations — directly causes foot process effacement and massive proteinuria.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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