A 16-year-old boy has hematuria and progressive proteinuria. His mother had persistent microscopic hematuria but normal renal function. The genetic defect most likely responsible for his disease is a mutation in:

• A COL4A3 on chromosome 2q36
• B COL4A5 on chromosome Xq22 ✓
• C NPHS2 encoding podocin
• D CFH encoding complement factor H

Explanation

Classic Alport syndrome follows X-linked dominant inheritance in about 85 percent of cases due to mutation of COL4B5 encoding the alpha-5 chain of type IV collagen. Affected males progress to ESRD, while heterozygous females usually have only hematuria, matching the pedigree here. Autosomal recessive Alport involves biallelic COL4B3 or COL4B4 mutations, inconsistent with the mother being mildly affected. NPHS2 mutations cause steroid-resistant FSGS and CFH defects cause atypical HUS or C3 glomerulopathy.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.