NPHS2 p.V290M mutation in late-onset steroid-resistant nephrotic syndrome

Pediatr Nephrol. 2013 May;28(5):751-7. doi: 10.1007/s00467-012-2379-2. Epub 2012 Dec 14.


Background: The most frequently mutated gene of steroid-resistant nephrotic syndrome (SRNS) is NPHS2. Current guidelines propose the sequencing of all NPHS2 exons only in childhood-onset SRNS.

Methods: A cohort of 38 Hungarian patients with childhood-onset nephrotic-range proteinuria was screened for NPHS2 mutations. The frequency of the p.V290M mutation in late-onset SRNS was examined in the French and PodoNet cohorts.

Results: Of the 38 Hungarian patients screened, seven carried NPHS2 mutations on both alleles, of whom two-diagnosed with proteinuria through school screening programs at the age of 9.7 and 14 years, respectively-did not develop nephrotic syndrome in childhood. The first, an 18-year-old boy, homozygous for p.V290M, has never developed edema. The second, a 31-year-old woman-compound heterozygous for p.V290M and p.R138Q-was first detected with hypoalbuminemia (<30 g/l) and edema at the age of 24.3 and 27.5 years, respectively. Both patients currently have a normal glomerular filtration rate. The mutation p.V290M was carried by three of the 38 patients in the Hungarian cohort, by two of the 95 patients with late-onset SRNS in the PodoNet cohort and by none of the 83 patients in the French cohort.

Conclusions: We propose that not only the p.R229Q variant, but also the p.V290M mutation should be screened in Central and Eastern European patients with late-onset SRNS.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Europe / epidemiology
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Testing / methods
  • Glomerular Filtration Rate
  • Haplotypes
  • Heterozygote
  • Homozygote
  • Humans
  • Infant
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Kidney / physiopathology
  • Male
  • Membrane Proteins / genetics*
  • Mutation, Missense*
  • Nephrotic Syndrome / congenital*
  • Nephrotic Syndrome / diagnosis
  • Nephrotic Syndrome / epidemiology
  • Nephrotic Syndrome / genetics
  • Nephrotic Syndrome / physiopathology
  • Phenotype
  • Proteinuria / genetics


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

Supplementary concepts

  • Nephrotic syndrome, idiopathic, steroid-resistant