A young man has hematuria, sensorineural hearing loss, and ocular abnormalities (anterior lenticonus). Renal biopsy electron microscopy shows 'basket-weave' (irregular thinning and splitting) of the glomerular basement membrane. The underlying molecular defect is:

• A Mutations in COL4A3, COL4A4, or COL4A5 genes encoding type IV collagen alpha chains ✓
• B Deletions in LAMB2 encoding laminin beta-2
• C Mutations in MYH9 (myosin heavy chain) encoding platelet cytoskeletal protein
• D ACTN4 mutations destabilizing glomerular endothelial cells

Explanation

Alport syndrome is caused by mutations in COL4A3 (chromosome 2), COL4A4 (chromosome 2), or COL4A5 (X-linked, chromosome X) — genes encoding the alpha3, alpha4, and alpha5 chains of type IV collagen that form the predominant isoform in the GBM. The abnormal GBM undergoes characteristic electron microscopic basket-weave splitting. Laminin beta-2 mutations cause Pierson syndrome (congenital nephrotic syndrome with ocular anomalies). MYH9 mutations cause May-Hegglin anomaly with macro-thrombocytopenia.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.