Mutations in the Wilms' tumor 1 gene cause isolated steroid resistant nephrotic syndrome and occur in exons 8 and 9

Bettina Mucha, Fatih Ozaltin, Bernward G. Hinkes, Katrin Hasselbacher, Rainer G. Ruf, Michael Schultheiss, Daniela Hangan, Bethan E. Hoskins, Anne Schulze Everding, Radovan Bogdanovic, Thomas Seeman, Bernd Hoppe, Friedhelm Hildebrandt, J. Thaarup, A. Noyan, A. Bakkaloglu, S. Kalman, J. Hopcian, K. Van Hoeck, G. GormanF. Burkhalter, B. Descoendres, M. Mayr, A. Peco-Antic, J. Putnik, N. Stajic, S. Briese, J. Gellermann, U. Querfeld, H. Bachmann, J. Springate, G. Reusz, A. Goldberg, C. Licht, D. Michalk, L. Stapenhorst, M. Gahr, G. Kvaldova, M. Laaß, W. Rascher, P. Hoyer, U. Neyer, M. Brandis, A. Fuchshuber, C. Von Schnakenburg, C. Mache, L. Patzer, M. Kemper, D. E. Müller-Wiefel, J. H.H. Ehrich, D. Hohmann, G. Offner, S. Skalova, F. Schäfer, T. Knüppel, O. Mehls, B. Tönshoff, D. Wenning, H. Patzer, G. Rönnefarth, R. Cohen-Becker, J. Scheinman, S. Hashmi, P. Eggert, R. Ettenger, L. Rangel, S. Wygoda, R. Beetz, F. Anacleto, H. Fehrenbach, K. Timmermann, M. Griebel, G. Filler, S. Pavicevic, J. Muscheites, G. Warnecke, N. Benador, J. Monterrode Pina Neto, M. Lilova, M. Bald, M. Holder, H. Leichter, A. Zolotnitskaya, R. Weiss, A. Pollak, G. Laube, T. Neuhaus

Research output: Contribution to journalArticlepeer-review

109 Scopus citations


Primary steroid-resistant nephrotic syndrome (SRNS) is characterized by childhood onset of proteinuria and progression to end-stage renal disease. Approximately 10-25% of familial and sporadic cases are caused by mutations in NPHS2 (podocin). Mutations in exons 8 and 9 of the WT1 gene have been found in patients with isolated SRNS and in SRNS associated with Wilms' tumor (WT) or urogenital malformations. However, no large studies have been performed to date to examine whether WT1 mutations in isolated SRNS are restricted to exons 8 and 9. To address this question, we screened a worldwide cohort of 164 cases of sporadic SRNS for mutations in all 10 exons of the WT1 gene by multiplex capillary heteroduplex analysis and direct sequencing. NPHS2 mutations had been excluded by direct sequencing. Fifteen patients exhibited seven different mutations exclusively in exons 8 and 9 of WT1. Although it is possible that pathogenic mutations of WT1 may also reside in the introns, regions of the gene that were not able to be screened in this study, these data together with our previous results (Ruf et al.: Kidney Int 66: 564-570, 2004) indicate that screening of WT1 exons 8 and 9 in patients with sporadic SRNS is sufficient to detect pathogenic WT1 mutations and may open inroads into differential therapy of SRNS.

Original languageEnglish (US)
Pages (from-to)325-331
Number of pages7
JournalPediatric Research
Issue number2
StatePublished - Feb 2006
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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