A WNT4 mutation associated with Müllerian-duct regression and virilization in a 46,XX woman.
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.
Biason-Lauber
Anna
A
Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, Zurich, Switzerland. anna.lauber@kispi.unizh.ch
Konrad
Daniel
D
Navratil
Francesca
F
Schoenle
Eugen J
EJ
D000293:Adolescent; D000568:Amenorrhea; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007621:Karyotyping; D009095:Mullerian Ducts / Q000002:abnormalities*; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013577:Syndrome; D014564:Urogenital Abnormalities / Q000235:genetics*; D014770:Virilism / Q000235:genetics*; D051153:Wnt Proteins; D060528:Wnt4 Protein
D011518:Proto-Oncogene Proteins; C555581:WNT4 protein, human; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse