title: WT1 deletion leading to severe 46,XY gonadal dysgenesis, Wilms tumor and gonadoblastoma: case report.
abstract: BACKGROUND
  Heterozygous missense mutations in the WT1 gene that affect the function of the wild-type allele have been identified in Denys-Drash syndrome, which is characterized by severe gonadal dysgenesis, early-onset nephropathy and a predisposition to renal and gonadal cancer. Intron 9 splice-site mutations that influence the balance between WT1 isoforms cause a nearly similar phenotype, known as Frasier syndrome. Nonsense mutations and deletions only lead to WT1 haploinsufficiency and, hence, to less severe gonadal dysgenesis and late-onset nephropathy. WT1 analysis is mandatory in 46,XY gonadal dysgenesis with renal abnormality.
  
  
  METHODS
  We describe a newborn with 46,XY severe partial gonadal dysgenesis, in whom structural renal anomalies and proteinuria were excluded. Gonadectomy was performed at the age of 1 month and the microscopy was thought to be suggestive for a gonadoblastoma. At the age of 9 months, the patient presented with a bilateral Wilms tumor.
  
  
  RESULTS
  We found a heterozygous WT1 whole-gene deletion but no other gene defects.
  
  
  CONCLUSIONS
  This case description illustrates that a WT1 deletion might be associated with a more severe phenotype than previously thought. It also illustrates that, even in the absence of renal abnormality, it is recommended to test promptly for WT1 defects in 46,XY gonadal dysgenesis.
authors.affiliation: Department of Pediatric Endocrinology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Martijn J J
authors.initials: MJ
authors.lastname: Finken
authors.forename: Yvonne M C
authors.initials: YM
authors.lastname: Hendriks
authors.forename: J Patrick
authors.initials: JP
authors.lastname: van der Voorn
authors.forename: Margreet A
authors.initials: MA
authors.lastname: Veening
authors.forename: M Paola
authors.initials: MP
authors.lastname: Lombardi
authors.forename: Joost
authors.initials: J
authors.lastname: Rotteveel
mesh_terms: D005260:Female; D017353:Gene Deletion; D006061:Gonadal Dysgenesis, 46,XY / Q000235:genetics*; D018238:Gonadoblastoma / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D016609:Neoplasms, Second Primary / Q000235:genetics*; D025721:WT1 Proteins / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics*
chemical_list: D025721:WT1 Proteins; C583751:WT1 protein, human