Pediatric Nephrology

, Volume 26, Issue 8, pp 1311–1315 | Cite as

A novel WT1 heterozygous nonsense mutation (p.K248X) causing a mild and slightly progressive nephropathy in a 46,XY patient with Denys–Drash syndrome

  • Thatiana Evilen da Silva
  • Mirian Yumie Nishi
  • Elaine Maria Frade Costa
  • Regina Matsunaga Martin
  • Filomena Marino Carvalho
  • Berenice Bilharinho Mendonca
  • Sorahia Domenice
Brief Report


WT1 mutations have been described in a variety of syndromes, including Denys-Drash syndrome (DDS), which is characterized by predisposition to Wilms’ tumor, genital abnormalities and development of early nephropathy. The most frequent WT1 defects in DDS are missense mutations located in exons 8-9. Our aim is to report a novel WT1 mutation in a 46,XY patient with a DDS variant, who presented a mild nephropathy with a late onset diagnosed during adolescence. He had ambiguous genitalia at birth. At 4 months of age he underwent nephrectomy (Wilms’ tumor) followed by chemotherapy. Ambiguous genitalia were corrected and bilateral gonadectomy was performed. Sequencing of WT1 identified a novel heterozygous mutation (c.742A>T) in exon 4 that generates a premature stop codon (p.K248X). Interestingly, this patient has an unusual DDS nephropathy progression, which reinforces that patients carrying WT1 mutations should have the renal function carefully monitored due to the possibility of late-onset nephropathy.


Denys-Drash syndrome WT1 gene Wilms’ tumor proteinuria 


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Copyright information

© IPNA 2011

Authors and Affiliations

  • Thatiana Evilen da Silva
    • 1
  • Mirian Yumie Nishi
    • 1
  • Elaine Maria Frade Costa
    • 1
  • Regina Matsunaga Martin
    • 1
  • Filomena Marino Carvalho
    • 2
  • Berenice Bilharinho Mendonca
    • 1
  • Sorahia Domenice
    • 1
  1. 1.Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM42Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao PauloSao PauloBrazil
  2. 2.Departamento de PatologiaFaculdade de Medicina da Universidade de Sao PauloSao PauloBrazil

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