Mutations in the human R-spondin homolog (RSPO1) gene, which encodes a WNT pathway adapter molecule, indicate that this molecule is also a primary female sex-determining factor (9).
XX individuals with a mutant RSPO1 gene exhibit testicular-like gonads, lack Müllerian structures (oviduct and uterus), and present masculinized external genitalia as a consequence of testicular androgen biosynthesis.