A WNT4 mutation associated with Müllerian-duct regression and virilization in a 46,XX woman

N Engl J Med. 2004 Aug 19;351(8):792-8. doi: 10.1056/NEJMoa040533.


WNT4, a secreted protein that suppresses male sexual differentiation, is thought to repress the biosynthesis of gonadal androgen in female mammals. An 18-year-old woman presented with primary amenorrhea and an absence of müllerian-derived structures, unilateral renal agenesis, and clinical signs of androgen excess--a phenotype resembling the Mayer-Rokitansky-Küster-Hauser syndrome and remarkably similar to that of female Wnt4-knockout mice. A genetic evaluation revealed a loss-of-function mutation in the WNT4 gene. WNT4 appears to be important in the development and maintenance of the female phenotype in women, by means of the regulation of müllerian-duct formation and control of ovarian steroidogenesis.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amenorrhea
  • DNA Mutational Analysis
  • Female
  • Humans
  • Karyotyping
  • Mullerian Ducts / abnormalities*
  • Mutation
  • Proto-Oncogene Proteins / genetics*
  • Syndrome
  • Urogenital Abnormalities / genetics*
  • Virilism / genetics*
  • Wnt Proteins
  • Wnt4 Protein


  • Proto-Oncogene Proteins
  • WNT4 protein, human
  • Wnt Proteins
  • Wnt4 Protein
  • Wnt4 protein, mouse