A 22-year-old woman is found to have persistent microscopic hematuria on a routine urine examination. Her renal function is normal, proteinuria is absent, and there is no hearing loss or ocular abnormality. Renal biopsy shows normal light microscopy and immunofluorescence. Electron microscopy shows uniformly thinned glomerular basement membranes measuring about 180 nm (normal 300 to 400 nm). The most likely underlying genetic defect is:

• A Heterozygous mutation in COL4A3 or COL4A4 ✓
• B Hemizygous mutation in COL4A5
• C Homozygous mutation in the nephrin gene (NPHS1)
• D Mutation in the alpha-galactosidase A gene

Explanation

Thin basement membrane lesion (benign familial hematuria) results from a heterozygous mutation in COL4A3 or COL4A4 encoding the alpha3 or alpha4 chain of type IV collagen. It follows autosomal dominant inheritance and carries an excellent prognosis. Homozygous or compound heterozygous mutations in these same genes produce Alport syndrome, while hemizygous COL4A5 mutation produces the common X-linked form of Alport syndrome, which features GBM splitting, deafness and ocular lesions, all absent here.

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.