The Wilms' tumour 1 gene as a factor in non-syndromic hypospadias: evidence and controversy

Pathology. 2018 Jun;50(4):377-381. doi: 10.1016/j.pathol.2017.12.341. Epub 2018 May 7.


Hypospadias is one of the most frequent congenital anomalies of the male external genitalia. Its pathogenesis is due to largely unknown or poorly understood genetic factors and is further complicated by environmental-intrauterine-risk factors. One of the genes currently in focus by molecular biologists and clinicians studying syndromic forms of hypospadias is the Wilms' tumour 1 (WT1) gene. There is controversy over whether WT1 defects are also responsible for isolated hypospadias. In this review, we briefly cover the role of WT1 as a transcription factor and discuss proposed pathogenic pathways leading to hypospadias, outlining possible directions for research. We assess available evidence on the gene's mutations and polymorphisms recently suggested in the background of the disease, and examine the putative role of WT1-associated proteins. We also review relevant aspects of genome-wide association studies carried out so far, and raise some points to consider in future efforts.

Keywords: Hypospadias; WT1 gene; WTAP gene; WTIP gene; rs2234583.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Cycle Proteins
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation / genetics*
  • Genome-Wide Association Study
  • Humans
  • Kidney Neoplasms / genetics*
  • Nuclear Proteins / genetics*
  • RNA Splicing Factors
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • RNA Splicing Factors
  • Transcription Factors
  • WTAP protein, human