title: Abnormal WT1 expression in human fetuses with bilateral renal agenesis and cardiac malformations.
abstract: BACKGROUND
  Bilateral renal agenesis has multiple etiologies. Animal models have provided useful information on possible causes of this condition, but its etiology in humans is less clear. We recently described autopsy findings of two human fetuses with bilateral renal agenesis and abnormal expression of WT1 (Wilms tumor 1) in liver mesothelium.
  
  
  METHODS
  We have identified 14 additional fetuses with bilateral renal agenesis from autopsies performed in our institution over the past 10 years and subjected archival liver biopsy specimens from these cases to immunohistochemistry for WT1, as well as α-smooth muscle actin (α-SMA) and desmin to assess liver mesenchymal abnormalities.
  
  
  RESULTS
  Six of seven fetuses with combined bilateral renal agenesis and cardiac anomalies showed abnormalities of WT1 expression in liver mesothelial cells, which was not seen in other fetuses with bilateral renal agenesis. Except in one case, the fetuses with renal agenesis and cardiac defects also showed liver mesenchymal anomalies (assessed by increased α-SMA expression), which was not present in other renal agenesis fetuses.
  
  
  CONCLUSIONS
  WT1 is widely expressed in mesothelial cells during development, and we hypothesized that some of the defects are caused by abnormal function of mesenchyme derived from mesothelial cells, similar to the mesothelium-derived defects proposed in animal models. The methods we used are available to many laboratories and can be applied to archival paraffin tissue blocks. We suggest that future similar studies could help to expand the understanding of renal agenesis in humans and could help to subclassify this condition. This would be useful in patient management and counseling.
authors.affiliation: Department of Anatomical Pathology, Royal Brisbane and Women's Hospital, Brisbane, Australia. Christine.Loo@qimr.edu.au
authors.forename: Christine K C
authors.initials: CK
authors.lastname: Loo
authors.forename: Tamara N
authors.initials: TN
authors.lastname: Pereira
authors.forename: Grant A
authors.initials: GA
authors.lastname: Ramm
mesh_terms: D001344:Autopsy; D000013:Congenital Abnormalities / Q000378:metabolism / Q000473:pathology*; D003893:Desmin / Q000378:metabolism; D004848:Epithelium / Q000002:abnormalities* / Q000378:metabolism* / Q000473:pathology; D005333:Fetus / Q000002:abnormalities*; D005865:Gestational Age; D006330:Heart Defects, Congenital / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000151:congenital* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000166:cytology / Q000378:metabolism; D025721:WT1 Proteins / Q000378:metabolism*
chemical_list: D003893:Desmin; D025721:WT1 Proteins