The authors of a new study suggest that all children with steroid-resistant nephrotic syndrome should be screened for mutations in the WT1 gene. Lipska and colleagues found that among 761 patients with this disease, those with mutations in WT1 (n = 61) more often presented with hypertension and chronic kidney disease at diagnosis and showed faster disease progression. Missense substitutions in WT1 that affected DNA-binding residues were associated with diffuse mesangial sclerosis and early onset of steroid-resistant nephrotic syndrome with rapid progression to end-stage renal disease (ESRD). By contrast, truncating mutations in WT1 were associated with late onset of steroid-resistant nephrotic syndrome and the highest risk of Wilms tumour, whereas intronic mutations were most likely to cause isolated steroid-resistant nephrotic syndrome, focal segmental glomerulosclerosis and slow progression to ESRD.