X-Linked Adrenal hypoplasia congenita: Clinical spectrum and molecular analysis of DAX1

DAX1 (dosage sensitive sex reversal-DSS) an important protein encoded by the gene NR0B1 (orphan nuclear receptor) located in a specific region on the X chromosome. This protein is a well studied molecular candidate involved in Adrenal gland development and also responsible for steroidogenesis in adults. It is expressed throughout the hypothalamic–pituitary–adrenal–gonadal (HPAG) axis, suggesting its pivotal role in early human sexual development. It potentially interacts with many important cellular receptors like androgen receptor (AR), estrogen receptor (ER) and progesterone receptor (PR). But, each of them are regulated by different mechanisms. However, the molecular mechanism of DAX1 in multiple stages of development is inadequately understood. Recent research reports on experimental animals, highlight that the Dax1 can be alternatively spliced suggesting that the functional role of Dax1 is more diverse and complex. Familial mutations in DAX1 are often associated with the pathological conditions like Adrenal hypoplasia congenita (AHC), hypogonadotropic hypogonadism (HH). Unlike the mutations, the duplication of this gene resulting in dosage sensitive sex reversal (DSS). Adrenal failure is the most significant phenotype of AHC resulting in glucocorticoid and mineralocorticoid deficiency subsequently influences the developmental transition of adult from fetus. In this review, we summarize the molecular background of DAX1, biological function, impact of its mutation in AHC formation and clinical significance of the protein expression in HH.

Keywords:

DAX1 , NR0B1 , Nuclear receptor , Adrenal hypoplasia congenita (AHC) , Hypogonadotropic hypogonadism (HH)