Biason-Lauber Anna, Konrad Daniel, Navratil Francesca, Schoenle Eugen J
Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, Zurich, Switzerland.
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.
WNT4是一种抑制雄性性分化的分泌蛋白，被认为在雌性哺乳动物中可抑制性腺雄激素的生物合成。一名18岁女性出现原发性闭经，缺乏苗勒管衍生结构、单侧肾缺如以及雄激素过多的临床体征——这种表型类似于 Mayer-Rokitansky-Küster-Hauser 综合征，与雌性Wnt4基因敲除小鼠的表型极为相似。基因评估显示WNT4基因存在功能丧失性突变。WNT4似乎通过调节苗勒管形成和控制卵巢类固醇生成，在女性女性表型的发育和维持中发挥重要作用。
