A 22-year-old man has persistent microscopic hematuria detected on routine examination. Blood pressure and renal function are normal; there is no proteinuria, no hearing loss, and no family history of kidney failure. Renal biopsy shows normal light microscopy and immunofluorescence. Electron microscopy shows uniformly attenuated glomerular basement membranes measuring approximately 180 nm. What is the most likely underlying defect?

• A Heterozygous mutation in COL4A3 or COL4A4 ✓
• B Homozygous mutation in the NPHS1 gene encoding nephrin
• C Mutation in the NC1 domain of the alpha 5 chain of type IV collagen affecting the epidermal basement membrane
• D Autoantibodies against the alpha 3 chain of type IV collagen

Explanation

Diffuse thinning of the GBM with isolated hematuria, preserved renal function, and absence of extrarenal features defines thin basement membrane nephropathy (benign familial hematuria), caused by heterozygous COL4B3 or COL4B4 mutations inherited in an autosomal dominant fashion. Alport syndrome (option C) involves COL4B5 in the classic X-linked form and produces GBM splitting with hearing loss and ocular lesions, not isolated uniform thinning.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.