Objective: To understand WT1 mutations in patients with steroid resistant nephrotic syndrome (SRNS) accompanied with genitourinary malformations.
Methods: Three cases of SRNS accompanied with genitourinary malformations were enrolled. The expression of podocyte molecules (nephrin, podocin, alpha-actinin-4, WT1, and CD2AP) in 2 cases was analyzed with the immunofluorescence and immunohistochemistry techniques. The genomic DNA and cDNA of WT1 were analyzed by using PCR and RT-PCR, respectively. GeneScan and GeneScan software were used to quantify the ratio of +KTS/-KTS isoforms.
Results: The onset ages of 3 cases were 6 months, 1 year, and 10 years old, respectively. The diagnosis age was 7 months, 9 years, and 15 years old, respectively. The phenotype of Case 1 and Case 3 was male accompanied with genitourinary malformations. Case 2 was phenotypic female. Karyotype analysis of 3 cases revealed 46, XY. Three cases were diagnosed as SRNS. Focal segmental glomerulosclerosis (FSGS) was confirmed in 2 cases. Podocyte molecular expression altered in renal tissues of 2 cases. In addition, WT1 staining was negative in Case 1. WT1 expression in Case 2 showed diffuse nuclear staining with less obvious speckles compared with controls. WT1 IVS 9 +5 G>A mutation was detected in Case 2 and WT1 Exon 9 1186 G>A mutation was detected in Case 3. No WT1 mutation was detected in Case 1.
Conclusion: Karyotype analysis and WT1 genetic testing should be done in all female patients with early onset steroid resistant FSGS and in male patients with SRNS accompanied with genitourinary malformations. Abnormal podocyte molecular expression suggests that more podocyte molecules might be involved in the pathogenesis of proteinuria in WT1 mutational patients.