A novel Wilms’ tumor 1 gene mutation in a child with severe renal dysfunction and persistent renal blastema


The Wilms’ tumor suppressor gene WT1 is an important regulator of development. Mutations in this gene have been associated with Wilms’ tumor, Frasier syndrome, and Denys–Drash syndrome, as well as isolated glomerular disease. Here we report the case of a 4-month-old girl, who presented with end-stage renal disease, thrombopenia, anemia, and cardiac hypertrophy accompanied by severe hypertension. Histological analysis of kidney biopsies revealed a massive and diffuse nephroblastomatosis with a dramatic reduction in the number of glomeruli. Although no normal cortical nephrons could be detected, medullary organization was nearly normal. Sequence analysis demonstrated a heterozygous nonsense mutation in exon 9 of WT1, which leads to a truncation of the WT1 protein at the beginning of zinc finger 3. Given the requirement of WT1 for normal development of the kidney and heart, these data raise the hypothesis that the mutation identified was responsible for the severe phenotype observed in our patient.

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The authors thank Marie Claire Gubler for the kidney control tissue of a 2-month-old child. This work was supported by grants from Fondation pour la Recherche médicale (FRM), EuReGene (EU), FP6 and L’Agence Nationale de la Recherche (ANR) (ANR-05-MRAR-019-01). N.W. is a fellow of Fondation - de France.

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Correspondence to Andreas Schedl or Etienne Berard.

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Wagner, N., Wagner, KD., Afanetti, M. et al. A novel Wilms’ tumor 1 gene mutation in a child with severe renal dysfunction and persistent renal blastema. Pediatr Nephrol 23, 1445–1453 (2008). https://doi.org/10.1007/s00467-008-0845-7

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  • Nephroblastomatosis
  • Wilms’ tumor suppressor gene
  • End-stage renal disease
  • Hypertension
  • Cardiac hypertrophy