Genetic screening in children with challenging nephrotic syndrome

Saudi J Kidney Dis Transpl. 2020 Nov-Dec;31(6):1189-1197. doi: 10.4103/1319-2442.308327.


Genetic screening paradigms for the nephrotic syndrome (NS) in the developed world are well established; however, screening in developing countries has received only minor attention. We retrospectively analyzed a cohort of all children who underwent genetic testing for challenging NS from our registry in the 10-year interval from 2000 to 2010 and based on 58 patients aged 0-12 years with at least one of the following clinical diagnosis: Nonsyndromic steroid-resistant nephrotic syndrome (SRNS), familial NS, and congenital NS. Of these, 23 patients (~40%) had a history of familial disease occurrence. All cases were screened for NPHS2 and WT1 mutations by direct sequencing of all exons of the genes. In addition, all patients who were diagnosed during the first three months of life were screened for NPHS1 mutations too. A genetic disease cause was identified in 12 patients (20.7%); of these, five novel mutations, all in NPHS2 accounting for 42% of all mutations and 9% of the cohort. Nine patients were found to have NPHS2 mutations. Only one case with SRNS had a mutation in WT1. Of the five congenital NS, two cases were found to have NPHS1 mutations and one case with NPHS2 mutation. Therefore, mutations in NPHS2 were the most commonly identified and explained in 15.5% of the screened patients and WT1 mutation in 1.7% of cases, whereas NPHS1 mutations were found in 40% of congenital NS cases. A genetic disease cause was identified in 20.7% of the screened patients. Among 12 identified mutations, abnormalities in NPHS2 (n = 9) were most commonly identified.

MeSH terms

  • Child
  • Child, Preschool
  • Female
  • Genetic Testing
  • Humans
  • Infant
  • Infant, Newborn
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Mutation
  • Nephrotic Syndrome / congenital*
  • Nephrotic Syndrome / drug therapy
  • Nephrotic Syndrome / genetics*
  • Retrospective Studies
  • Steroids / therapeutic use
  • WT1 Proteins / genetics*


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

Supplementary concepts

  • Nephrosis, congenital
  • Nephrotic syndrome, idiopathic, steroid-resistant