WT1 mutation-associated nephropathy: asingle-center experience .

Abstract

This study explored Wilms' tumor 1 (<i>WT1</i>) mutations in children with, or suspected of having, steroid-resistant nephrotic syndrome (SRNS), referred to or treated in our hospital in the past 6 years as well as the correlation between genotype and phenotype in <i>WT1</i> mutation-associated nephropathy in Chinese patients. In total, 76 patients participated in the study. <i>WT1</i> mutations were identified in 15 patients, 5 of whom harbored splice-site mutations in intron 9. Four of these 5 patients exhibited early onset of nephropathy and rapid deterioration of renal function. Missense mutations were detected in 8 patients, 4 of whom harbored hot-site mutations and had early-onset proteinuria. Of these 4 patients, rapid progression to end-stage renal disease was only observed in 1. Nonsense mutations were identified in 2 patients; both had a large number of immature glomeruli in the kidney cortex. Calcineurin inhibitors (CNI) were administered in 8 patients. Two patients with missense mutations and 1 patient with a nonsense mutation achieved complete remission. Two patients with missense mutations and 2 with splice-site mutations showed an improvement. One patient with a splice-site mutation showed no changes. In conclusion, a high <i>WT1</i> mutation rate was observed in this group of SRNS patients. Patients with splice-site mutations experienced a rapid disease progression, and patients harboring nonsense mutations showed a prominent glomerular developmental delay. CNI therapy was effective in patients with <i>WT1</i> missense mutations and nonsense mutations. .