A WNT4 mutation associated with Mullerian-duct regression and virilization in a 46,XX woman
A WNT4 mutation associated with Mullerian-duct regression and virilization in a 46,XX woman
复制标题
DOI：
10.1056/nejmoa040533
复制
发表时间：
2004-08-19
影响因子：
158.5
通讯作者：
Schoenle, EJ
中科院分区：
文献类型：
--
作者：
Biason-Lauber, A;Konrad, D;Schoenle, EJ
WNT4 是一种抑制雄性性别分化的分泌蛋白，被认为可以抑制雌性哺乳动物性腺雄激素的生物合成。一名 18 岁女性出现原发性闭经、苗勒氏管衍生结构缺失、单侧肾发育不全以及雄激素过多的临床症状，这种表型类似于 Mayer-Rokitansky-Kuster-Hauser 综合征，并且与雌性 Wnt4 基因敲除小鼠的表型非常相似。遗传评估显示 WNT4 基因存在功能丧失突变。 WNT4 通过调节苗勒管形成和控制卵巢类固醇生成，在女性表型的发育和维持中发挥着重要作用。
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.