WT1 and NPHS2 gene mutation analysis and clinical management of steroid-resistant nephrotic syndrome

Abstract

Nephrotic syndrome (NS) is a kidney disease predominantly present in children with idiopathic condition; final stage of the disease progresses into end-stage renal disease. Generally, NS is treated using standard steroid therapy, however; most of the children are steroid sensitive and about 15-20% are non-responders (SRNS). Non-responsiveness of these children would be a risk with the possibility of mutational changes in podocyte genes (NPHS1, NPHS2, WT1, PLCE1). The mutation in podocyte genes is associated with SRNS. NPHS1, NPHS2, and WT1 genes are identified/directly linked to SRNS. The present study is a surveillance on the mutation analysis of WT1 (exons 8 and 9) and NPHS2 (exons 1-8) gene in SRNS followed by clinical management. In the present study, we analyzed these two genes in a total of 117 SRNS (73 boys and 44 girls) children. A total of five mutations were detected in six children. First, WT1 mutation was detected at 9th intron-IVS 9 + 4C > T position in one SRNS female patient. This WT1 mutation was identified in a girl having Frasier Syndrome (FS) with focal segmental glomerulosclerosis and a complete sex reversal found through molecular and karyological screening. In NPHS2, missense mutations of P20L (in two children), P316S, and p.R229Q, and a frame shift mutation of 42delG were detected. Thus, applying molecular investigation helped us to decide on treatment plan of SRNS patients, mainly to avoid unnecessary immunosuppressive treatment.

The podocin V260E mutation predicts steroid resistant nephrotic syndrome in black South African children with focal segmental glomerulosclerosis

“…In their study, APOL1 variants were not associated with NS, but the NPHS2 V260E allele was specifically associated with SRNS (with FSGS) in black children; 8 were homozygous for the variant (OR 21; 95% CI, 2.8–960) and no heterozygotes were observed. The NPHS2 V260E variant alters the podocin protein and prevents the movement of the protein to the plasma membrane, affecting the structural integrity of the slit diaphragm 21 . This variant was absent in the Indian children (cases and controls) and absent in all black children with SSNS.…”

Identification of key pathways and genes in different types of chronic kidney disease based on WGCNA

“…In addition, a novel intriguing co-expression module (the Yellow module) was also detected in this study, which contained genes involved in ‘glomerulus development’, ‘kidney development’ and ‘multicellular organismal development’ GO terms [e.g. NPHS1 (35), NPHS2 (36), WT1 (37), podocalyxin-like and PLCE1]. Since the Yellow module mainly contained genes downregulated in patients with CKD and was negatively correlated with CKD clinical traits; these results indicated that the renal parenchyma may be damaged in CKD and the corresponding repair mechanisms may be suppressed.…”

Correlation of TNF‑α and IL‑10 gene polymorphisms with primary nephrotic syndrome

“…Nephrotic syndrome is a disease with a complicated pathogenesis caused by heredity, infection and other factors, in which the immune microenvironment is often out of balance (13,14). Primary nephrotic syndrome is nephrotic syndrome without definite cause.…”