Mutations in DAX-1, an X-linked gene encoding an orphan nuclear receptor, have been associated with adrenal hypoplasia congenita and hypogonadotropic hypogonadism.
Mutations in the orphan nuclear receptor DAX1 (NR0B1) cause X-linked adrenal hypoplasia congenital (AHC), a disorder characterized by primary adrenal failure, hypogonadotropic hypogonadism. and azoospermia.
Here, we consider mutations in KAL in X-linked Kallmann syndrome; DAX1 in X-linked adrenal hypoplasia congenita; the related orphan nuclear receptor, steroidogenic factor-1; leptin and prohormone convertase-1, which may influence GnRH release and processing; the GnRH receptor; the pituitary transcription factors, HESX-1, LHX3 and PROP-1; and the gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH).
Mutations of the DAX1 gene (Dosage-sensitive sex reversal-Adrenal hypoplasia congenita critical region on the X chromosome gene 1), which encodes a novel orphan nuclear receptor, have been identified in patients with X-linked adrenal hypoplasia congenita (AHC) and hypogonadotrophic hypogonadism (HHG).
X-linked adrenal hypoplasia congenita (AHC) with hypogonadotropic hypogonadism was recently shown to be caused by mutations in a gene referred to as DAX-1, which encodes a novel member of the orphan nuclear receptor family.