NPHS2 mutations in steroid-resistant nephrotic syndrome: a mutation update and the associated phenotypic spectrum

Karim Bouchireb, Olivia Boyer, Olivier Gribouval, Fabien Nevo, Evelyne Huynh-Cong, Vincent Morinière, Raphaëlle Campait, Elisabet Ars, Damien Brackman, Jacques Dantal, Philippe Eckart, Maddalena Gigante, Beata S Lipska, Aurélia Liutkus, André Megarbane, Nabil Mohsin, Fatih Ozaltin, Moin A Saleem, Franz Schaefer, Kenza SoulamiRoser Torra, Nicolas Garcelon, Géraldine Mollet, Karin Dahan, Corinne Antignac

Research output: Contribution to journalArticle (Academic Journal)peer-review

55 Citations (Scopus)


Mutations in the NPHS2 gene encoding podocin are implicated in an autosomal-recessive form of nonsyndromic steroid-resistant nephrotic syndrome in both pediatric and adult patients. Patients with homozygous or compound heterozygous mutations commonly present with steroid-resistant nephrotic syndrome before the age of 6 years and rapidly progress to end-stage kidney disease with a very low prevalence of recurrence after renal transplantation. Here, we reviewed all the NPHS2 mutations published between October 1999 and September 2013, and also all novel mutations identified in our personal cohort and in international genetic laboratories. We identified 25 novel pathogenic mutations in addition to the 101 already described. The mutations are distributed along the entire coding region and lead to all kinds of alterations including 53 missense, 17 nonsense, 11 small insertions, 26 small deletions, 16 splicing, two indel mutations, and one mutation in the stop codon. In addition, 43 variants were classified as variants of unknown significance, as these missense changes were exclusively described in the heterozygous state and/or considered benign by prediction software. Genotype-phenotype analyses established correlations between specific variants and age at onset, ethnicity, or clinical evolution. We created a Web database using the Leiden Open Variation Database ( software that will allow the inclusion of future reports.

Original languageEnglish
Pages (from-to)178-86
Number of pages9
JournalHuman Mutation
Issue number2
Publication statusPublished - Feb 2014


  • Adult
  • Age of Onset
  • Animals
  • Child, Preschool
  • Disease Models, Animal
  • Genetic Variation
  • Genotype
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Mutation
  • Nephrotic Syndrome
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Software


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