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

Mol Cell Biochem. 2017 Feb;426(1-2):177-181. doi: 10.1007/s11010-016-2889-5. Epub 2016 Nov 25.

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.

Keywords: FSGS; Indian children; NPHS2; NS; SRNS; Wilms’ tumor.

MeSH terms

  • Child
  • Child, Preschool
  • Drug Resistance / genetics*
  • Female
  • Frameshift Mutation*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mutation, Missense*
  • Nephrotic Syndrome / drug therapy
  • Nephrotic Syndrome / genetics*
  • Nephrotic Syndrome / metabolism
  • Nephrotic Syndrome / pathology
  • Podocytes / metabolism
  • Podocytes / pathology
  • Steroids / therapeutic use
  • WT1 Proteins / genetics*
  • WT1 Proteins / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NPHS2 protein
  • Steroids
  • WT1 Proteins
  • WT1 protein, human