The orphan nuclear receptor that is encoded by the nuclear receptor subfamily 0 group B member 1 gene (NR0B1) is essential for the growth and control of the adrenal gland and hypothalamic-pituitary-gonadal axis. For a study, researchers sought to describe a new mutation in NR0B1 that resulted in adult-onset adrenal hypoplasia congenita (AHC) and lack of pubertal development in a male adult.

Clinical testing showed hyponatremia, raised adrenocorticotropic hormone levels, decreased levels of testosterone and gonadotropin, and hyper responses to tests using gonadotropin-releasing hormone and human chorionic gonadotropin stimulation. Sanger sequencing and whole-exome sequencing were used to find possible causes of AHC. X-linked recessive models were used to narrow down the number of potential mutations.

In exon 1 of NR0B1 at Xp21.2, sequence analysis discovered a unique hemizygous variation of c.1034delC, leading to a frameshift mutation and an early stop codon formation. The c.1034delC/p.Pro345Argfs*27 mutation in the NR0B1 gene was found to be heterozygous in healthy female family carriers and hemizygous in affected men.

The findings broadened the clinical characteristics of AHC and the mutational profile of the responsible gene, NR0B1. To fully understand the physiologic implications of the mutation on the growth and operation of the adrenal gland and the hypothalamic-pituitary-gonadal axis, more research is required.