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Published January 1, 2014 | Version v1
Journal article Open

NPHS2 Mutations in Steroid-Resistant Nephrotic Syndrome: A Mutation Update and the Associated Phenotypic Spectrum

Creators

  • 1. Hop Necker Enfants Malad, AP HP, Dept Genet, F-75015 Paris, France
  • 2. Univ Autonoma Barcelona, Mol Biol Lab, Inst Invest Biomed St Pau IIB St Pau, Fundacio Puigvert,REDinREN,Inst Invest Carlos III, E-08193 Barcelona, Spain
  • 3. Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway
  • 4. CHU Hotel Dieu, ITERT, Serv Nephrol & Immunol Clin, Nantes, France
  • 5. CHU Caen, Serv Pediat Med, F-14000 Caen, France
  • 6. Univ Foggia, Dept Med & Surg Sci, Foggia, Italy
  • 7. Med Univ Gdansk, Dept Biol & Genet, PL-80211 Gdansk, Poland
  • 8. Hop Femme Mere Enfant, Serv Nephrol & Rhumatol Pediat, Ctr Reference Malad Renales Rares, Bron, France
  • 9. Univ St Joseph, Fac Med, Unite Genet Med, Beirut, Lebanon
  • 10. Royal Hosp, Dept Nephrol, Muscat, Oman
  • 11. Hacettepe Univ, Fac Med, Nephrogenet Lab, Dept Pediat Nephrol, TR-06100 Ankara, Turkey
  • 12. Univ Bristol, Dept Paediat Nephrol, Bristol Royal Hosp Children, Acad Renal Unit,Sch Clin Sci, Bristol, Avon, England
  • 13. Heidelberg Univ, Ctr Pediat & Adolescent Med, PodoNet Consortium, Div Pediat Nephrol, Heidelberg, Germany
  • 14. CHU Ibn Rochd, Serv Nephrol Dialyse Transplantat, Casablanca, Morocco

Description

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 6years 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 (www.lovd.nl/NPHS2) software that will allow the inclusion of future reports. (C) 2013 Wiley Periodicals, Inc.

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