CFHR5 Nephropathy in a Greek-Cypriot Australian Family: Ancestry-Informed Precision Medicine

摘要

C3 glomerulopathy is caused by alternative com- plement pathway dysfunction, leading toabnormal complement activation, deposition, anddegradation in the glomerulus.1 This disorder manifestsas predominant glomerular C3 fragment deposition onimmunofluorescence, with absent or scant Ig deposition, and electron-dense deposits on electron microscopy.1 C3 glomerulopathy is subsequently classifiedinto dense deposit disease (DDD) and C3 glomerulonephritis (C3GN), based on ultrastructure. Lightmicroscopy of C3GN is more varied compared to DDD,with mesangial matrix expansion, mesangial proliferation, glomerular basement membrane thickening,endocapillary proliferation, leukocyte infiltration, andcrescent formation. Electron microscopy demonstratessubendothelial, subepithelial, and mesangial depositsthat are less electron dense and less confluentcompared with those in DDD. Patients with C3glomerulopathy can present with persistent microscopic hematuria, synpharyngitic macroscopichematuria, heavy proteinuria, and progressive renalimpairment.