An 8-year-old boy has persistent microscopic haematuria, bilateral sensorineural hearing loss, and anterior lenticonus. His mother has haematuria. Kidney biopsy electron microscopy shows alternating thickening and thinning of the glomerular basement membrane with splitting and lamellation. Which protein is defective?

• A Podocin
• B Type III collagen alpha-1 chain
• C Type IV collagen alpha-5 chain ✓
• D Alpha-actinin-4

Explanation

Alport syndrome results from mutations in COL4C5 encoding the alpha-5 chain of type IV collagen, inherited X-linked in about 85 percent of cases, which fits transmission from an affected mother. The triad of hereditary nephritis, sensorineural deafness, and ocular lesions such as lenticonus is characteristic, and EM shows the basket-weave lamellated GBM. Podocin and alpha-actinin-4 defects cause steroid-resistant FSGS, and type III collagen is unrelated to the GBM.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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