A 35-year-old woman presents with nephrotic syndrome. Renal biopsy shows uniform thickening of the GBM on light microscopy (silver stain — no spikes), negative IF for IgG/IgM/C3, and thin GBM with focal effacement on EM. Genetic testing reveals a mutation in NPHS2 (podocin). This pattern represents:

• A Membranous nephropathy (MN)
• B Focal segmental glomerulosclerosis (FSGS), genetic (podocin mutation) ✓
• C Alport syndrome (COL4A5 mutation)
• D Thin basement membrane disease

Explanation

NPHS2 encodes podocin, a critical scaffolding protein of the slit diaphragm complex. Autosomal recessive mutations in NPHS2 cause familial/genetic FSGS, presenting with nephrotic syndrome in children or young adults. Genetic FSGS is resistant to immunosuppression and progresses to end-stage renal disease. Membranous nephropathy shows subepithelial deposits with 'spikes' on silver stain and granular IgG/PLA2R+ on IF. Alport syndrome (COL4A5/COL4A3/COL4A4 mutations) presents with hematuria, high-tone sensorineural hearing loss, and characteristic GBM splitting on EM.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.