A WNT4 mutation associated with Mullerian-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 mullerian-derived structures, unilateral renal agenesis, and clinical signs of androgen excess - a phenotype resembling the Mayer - Rokitansky - Kuster - 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 mullerian-duct formation and control of ovarian steroidogenesis.