A 20-year-old man with sensorineural hearing loss and recurrent hematuria undergoes renal biopsy. Electron microscopy shows irregular thinning and thickening of the glomerular basement membrane with a characteristic 'basket-weave' splitting of the lamina densa. The underlying defect involves:

• A Fibrillin-1 gene mutation
• B Complement factor H mutation
• C Podocin gene mutation
• D Defective synthesis of type IV collagen alpha-3 or alpha-5 chains ✓

Explanation

Alport syndrome is caused by mutations in genes encoding type IV collagen alpha chains (most commonly COL4A5 on the X chromosome), leading to defective GBM assembly. The GBM normally transitions from alpha-1/alpha-2 to alpha-3/alpha-4/alpha-5 networks during development; absence of these chains results in the characteristic ultrastructural 'basket-weave' lamellation of the lamina densa. The triad of hematuria, sensorineural deafness, and ocular defects (anterior lenticonus) is classic.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.