A 25-year-old man has hematuria, proteinuria, and sensorineural hearing loss. His mother has the same condition. Electron microscopy shows 'basket-weave' lamellation of the GBM. The underlying genetic defect is:

• A NPHS2 mutation causing podocin deficiency
• B COL4A3/COL4A4/COL4A5 mutations — defective alpha chains of type IV collagen ✓
• C LAMB2 mutation causing laminin beta-2 deficiency
• D WT1 mutation causing Denys-Drash syndrome

Explanation

Alport syndrome is caused by mutations in COL4A5 (X-linked) or COL4A3/COL4A4 (autosomal), encoding type IV collagen alpha chains essential for GBM and cochlear basement membrane integrity. EM shows the characteristic 'basket-weave' (lamellation) of the GBM. The triad is progressive renal failure + sensorineural deafness ± anterior lenticonus. NPHS2 mutations cause FSGS; LAMB2 causes Pierson syndrome; WT1 mutations cause Denys-Drash syndrome.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.