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 suppress the synthesis of gonadal androgen in females. These investigators describe a woman with no müllerian-derived structures, unilateral renal agenesis, and clinical signs of androgen excess who had a loss-of-function mutation in the WNT4 gene. By regulating the formation of müllerian ducts, WNT4 appears to be crucial for the development of the female phenotype. The differentiation of a testis or an ovary from the bipotential gonad is a complex developmental process involving various genes and hormones. 1 Additional elements of the reproductive tract develop from an indeterminate stage through the differentiation of wolffian ducts (male reproductive tract anlage) and müllerian ducts (female reproductive tract anlage). Although factors involved in male sexual differentiation have been well studied, the pathways that regulate female sexual differentiation remain incompletely defined. To date, no genes have been shown to play a role in ovarian development equivalent to that played by the SRY or SOX9 gene in testicular development. In mice, . . .