A heterozygous intragenic duplication within the repeated area (CTGCAGCTG)×2 of the NR5A1 gene was found in a 15-year-old 46,XY DSD (disorders/differences of sex development) patient with micropenis and severe proximal hypospadias.
Mutations in NR5A1 were first described in patients with primary adrenal insufficiency and 46,XY disorders of sexual development and later also in men with hypospadias, bilateral anorchia and micropenis and women with primary ovarian insufficiency.
METHODS This study involved mutational analysis of NR5A1 in 24 individuals with bilateral anorchia and micropenis from the French Collaborative Anorchia study, as well as in vitro functional studies of SF1-dependent transcriptional activation and computer modeling.