Potential roles of wingless-type-MMTV integration site family, member 2 (WNT2) in human male external genital development

Abstract

In a large part of 46,XY patients with defective external genital differentiation neither alterations of androgen biosynthesis nor of androgen action can be detected. This supports that mechanisms independent from androgen signalling may be involved in male external genital development. Of note, outgrowth of the genital tubercle starts long before the onset of androgen production. HOXA13 mutations in hand-foot-genital syndrome are rare examples of primary defects of genital tubercle development. WNT2 is an intra-cellular signalling molecule that plays roles in sexual differentiation in Drosophila. In a previous microarray-based study, we demonstrated high expression of WNT2 in human foreskin fibroblasts suggesting roles of WNT2 in the human genital tubercle.