Thirteen novel NPHS1 mutations in a large cohort of children with congenital nephrotic syndrome

Saskia F. Heeringa, Christopher N. Vlangos, Gil Chernin, Bernward Hinkes, Rasheed Gbadegesin, Jinhong Liu, Bethan E. Hoskins, Fatih Ozaltin, Friedhelm Hildebrandt, A. Noyan, A. Bakkaloglu, S. Spranger, S. Briese, D. Müller, U. Querfeld, G. Reusz, R. Bogdanovic, B. Beck, B. Hoppe, M. T F WolfK. Dittrich, J. Dötsch, C. Plank, E. M. Rüth, W. Rascher, P. Hoyer, M. Schröder, M. Brandis, A. Fuchshuber, M. Pohl, C. V. Schnakenburg, C. Mache, F. Schäfer, T. Knüppel, O. Mehls, B. Tönshoff, D. Wenning, M. Kemper, D. E. Müller-Wiefel, J. H H Ehrich, G. Offner, M. Barenbrock, T. Jungraithmayr, B. Zimmerhackl, J. Misselwitz, S. Wygoda, D. Böckenhauer, M. Schuhmacher, M. Benz, M. Griebel, J. Höfele, L. Weber, H. Fehrenbach, M. Bulla, E. Kuwertz-Bröcking, A. Schulze Everding, M. Shenoy, L. Patzer, T. Seeman, A. Gianviti, G. Rizzoni, O. Amon, C. Licht, J. Mühleder, G. Laube, T. Neuhaus, T. Stuckert

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


Background. Congenital nephrotic syndrome (CNS) is de- fined as nephrotic syndrome that manifests at birth or within the first 3 months of life. Most patients develop end-stage renal disease (ESRD) within 2 to 3 years of life. CNS of the Finnish-type (CNF) features a rather specific renal histology and is caused by recessive mutations in the NPHS1 gene encoding nephrin, a major structural protein of the glomerular slit-diaphragm. So far, more than 80 different mutations of NPHS1 causing CNF have been published. Methods. Here, we performed mutation analysis of NPHS1 by exon sequencing in a worldwide cohort of 32 children with CNS from 29 different families. Results. Sixteen of the 29 families (55%) were found to have two disease-causing alleles in NPHS1. Two additional patients had a single heterozygous mutation in NPHS1. Thirteen of a total of 20 different mutations detected were novel (65%). These were five missense mutations, one nonsense mutation, three deletions, one insertion and three splice-site mutations. Conclusion. Our data expand the spectrum of known NPHS1 mutations by >15% in a worldwide cohort. Surprisingly, two patients with disease-causing mutations showed a relatively mild phenotype, as one patient had a partial remission with steroid treatment and one patient had normal renal function 1 year after the onset of disease. The increased number of known mutations will facilitate future studies into genotype/phenotype correlations.

Original languageEnglish (US)
Pages (from-to)3527-3533
Number of pages7
JournalNephrology Dialysis Transplantation
Issue number11
StatePublished - Nov 2008


  • CNS
  • NPHS1
  • Novel mutations

ASJC Scopus subject areas

  • Nephrology
  • Transplantation


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