Remarkably, in one family a sibling raised as a girl and carrying this NR5A1 mutation was found to have a 46,XY karyotype with partial testicular dysgenesis.
NR5A1 mutations have been identified in patients with various forms of 46,XY disorders of sex development (DSD), including complete gonadal dysgenesis with or without adrenal insufficiency, mild testicular dysgenesis with ambiguous external genitalia or female external genitalia with clitoromegaly, and penoscrotal hypospadias.
The frequency of NR5A1 mutations in otherwise unexplained 46,XY DSD with underandrogenization and partial testicular dysgenesis has been estimated to be about 15%.
Consequently, deletion of the gene (Nr5a1) encoding Sf-1 in XY mice results in impaired adrenal development, complete testicular dysgenesis with Mullerian structures, and female external genitalia.