NPHS2 (podicin) mutations in Turkish children with idiopathic nephrotic syndrome

Pediatr Nephrol. 2007 Dec;22(12):2031-40. doi: 10.1007/s00467-007-0595-y. Epub 2007 Sep 25.


The podocin (NPHS2) gene encodes podocin protein, which has an important role in glomerular ultrafiltration and controlling slit membrane permeability. The detection of an NPHS2 mutation affects the treatment plan for children with nephritic syndrome (NS). The frequency and spectrum of podocin mutations in the Turkish population have remained largely unknown. The aim of this study was to screen for podocin mutations in Turkish patients with steroid-resistant NS (SRNS) and to compare it with other published series. There were 295 children with SRNS, originating from Turkey, included in this study. Forty-one patients (13.8%) had familial NS and 254 patients (86.2%) had sporadic NS. Mutation analysis was performed in all eight exons of the NPHS2 gene with the direct DNA sequencing method. There were 53 different pathogenetic NPHS2 mutations detected, including 37 novel mutations. The mutation detection rate was 24.7% for all patients, 29.2% for familial, and 24% for sporadic SRNS. The most common mutated exon was exon 5 (52 allele). The presence of mutations in exon 4 was found to increase the risk of end-stage renal disease (ESRD). Among patients with mutations, the rates of renal failure and/or ESRD (26%) were significantly higher than in those without mutations (12.6%). The mean time of progression to renal failure and ESRD in patients with mutations (1.8 +/- 2.5 years) was significantly shorter than in patients without mutations (3.7 +/- 4.0 years). Additionally, in patients with heterozygote mutations, fewer cases (13.6%) progressed to renal failure and/or ESRD than in with patients who had homozygote/compound heterozygote mutations (31.3%). In conclusion, podocin mutations are responsible for some of both familial and sporadic SRNS cases in Turkey. The mutations in this gene should be searched for in every child after presentation with the first episode of NS.

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Glomerulosclerosis, Focal Segmental / complications
  • Glomerulosclerosis, Focal Segmental / genetics
  • Glomerulosclerosis, Focal Segmental / pathology
  • Humans
  • Infant
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Kidney / pathology
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / genetics
  • Kidney Failure, Chronic / pathology
  • Male
  • Membrane Proteins / genetics*
  • Mutation*
  • Nephrotic Syndrome / complications
  • Nephrotic Syndrome / genetics*
  • Nephrotic Syndrome / pathology
  • Turkey


  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NPHS2 protein