Pediatric Nephrology

, Volume 21, Issue 10, pp 1393–1398 | Cite as

WT1 mutations in nephrotic syndrome revisited. High prevalence in young girls, associations and renal phenotypes

  • Filippo Aucella
  • Luigi Bisceglia
  • Patrizia De Bonis
  • Maddalena Gigante
  • Gianluca Caridi
  • Giancarlo Barbano
  • Gerolamo Mattioli
  • Francesco Perfumo
  • Loreto Gesualdo
  • Gian Marco GhiggeriEmail author
Original Article


WT1 mutations have been considered a rare cause of nephrotic syndrome but recent reports challenge this assumption. Exclusion of inherited forms is a basic point in any therapeutic strategy to nephrotic syndrome since they do not respond to drugs. We screened for WT1 mutations in 200 patients with nephrotic syndrome: 114 with steroid resistance (SRNS) and 86 with steroid dependence (SDNS) for whom other inherited forms of nephrotic syndrome (NPHS2, CD2AP) had been previously excluded. Three girls out of 32 of the group with steroid resistance under 18 years presented classical WT1 splice mutations (IVS9+5G>A, IVS9+4C>T) of Frasier syndrome. Another one presented a mutation coding for an amino acid change (D396N) at exon 9 that is typical of Denys-Drash syndrome. All presented resistance to drugs and developed end stage renal failure within 15 years. Two girls of the Frasier group presented a 46 XY karyotype with streak gonads while one was XX and had normal gonad morphology. In the two cases with IVS9+5G>A renal pathology was characterized by capillary wall thickening with deposition of IgG and C3 in one that was interpreted as a membrane pathology. Foam cells were diffuse in tubule-interstitial areas. In conclusion, WT1 splice mutations are not rare in females under 18 years with SRNS. This occurs in absence of a clear renal pathology picture and frequently in absence of phenotype change typical of Frasier syndrome. In adults and children with SDNS, screening analysis is of no clinical value. WT1 hot spot mutation analysis should be routinely done in children with SRNS; if the molecular screening anticipates any further therapeutic approach it may modify the long term therapeutic strategy.


WT1 Nephrotic syndrome Focal segmental glomerulosclerosis Frasier syndrome Denys-Drash syndrome 



Focal segmental glomerulosclerosis


Frasier syndrome


Denys-Drash syndrome



This work was completed with the financial support of the Italian Ministry of Health and Fondazione Mara, Wilma e Bianca Querci (Project:‘’Nuove evoluzioni sulla multifattorialità della sindrome nefrosica’’).


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Copyright information

© IPNA 2006

Authors and Affiliations

  • Filippo Aucella
    • 1
  • Luigi Bisceglia
    • 2
  • Patrizia De Bonis
    • 2
  • Maddalena Gigante
    • 6
  • Gianluca Caridi
    • 3
  • Giancarlo Barbano
    • 4
  • Gerolamo Mattioli
    • 5
  • Francesco Perfumo
    • 4
  • Loreto Gesualdo
    • 6
  • Gian Marco Ghiggeri
    • 3
    Email author
  1. 1.Nephrology UnitIRCCS Casa Sollievo della SofferenzaSan Giovanni RotondoItaly
  2. 2.Medical Genetics ServiceIRCCS Casa Sollievo della SofferenzaSan Giovanni RotondoItaly
  3. 3.Laboratory on Pathophysiology of UremiaG. Gaslini Children’s HospitalGenoaItaly
  4. 4.Department of NephrologyG. Gaslini Children’s HospitalGenoaItaly
  5. 5.Department of Pediatric SurgeryG. Gaslini Children’s HospitalGenoaItaly
  6. 6.Department of Biomedical Sciences-Nephrology SectionUniversity of FoggiaFoggiaItaly

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