Alport syndrome is caused by mutations in genes encoding which glomerular basement membrane component, leading to progressive nephritis with sensorineural deafness?

• A Laminin beta-2 chain
• B Type IV collagen alpha-3/4/5 chains ✓
• C Fibronectin
• D Perlecan (heparan sulfate proteoglycan)

Explanation

Alport syndrome is caused by mutations in COL4A3, COL4A4 (autosomal), or COL4A5 (X-linked, most common) genes encoding type IV collagen alpha chains that form the network backbone of the GBM. The defective collagen also affects the cochlear basement membrane and ocular lens, explaining sensorineural deafness and anterior lenticonus. EM shows thinning, splitting, and lamellation of the GBM.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.