NR0B1

Several variants (also called mutations) in the NR0B1 gene have been found to cause X-linked adrenal hypoplasia congenita. This condition affects the development of the adrenal glands, which are endocrine organs (glands) located on top of each kidney. Some of the genetic changes are deletions of all or part of the NR0B1 gene. Other variants lead to the production of an abnormally short version of the DAX1 protein. Still other variants change single protein building blocks (amino acids) in a critical region of DAX1.

Most of the variants responsible for X-linked adrenal hypoplasia congenita prevent the NR0B1 gene from producing any active DAX1 protein. A shortage of DAX1 disrupts the normal development and function of endocrine tissues in the body.  The main characteristics of this condition result when endocrine glands such as the adrenals, hypothalamus, pituitary, and gonads do not produce the right amounts of specific hormones.

MedlinePlus Genetics provides information about Swyer syndrome

In some cases, genetic material is deleted from a region of the X chromosome that contains several genes, including NR0B1. This deletion results in a condition called adrenal hypoplasia congenita with complex glycerol kinase deficiency. In addition to the signs and symptoms of X-linked adrenal hypoplasia congenita (described above), individuals with this condition may have delayed development and problems regulating their blood sugar (glucose) levels. In rare cases, the deletion also includes the gene associated with Duchenne and Becker muscular dystrophy. People with this larger deletion have progressive muscle weakness and wasting in addition to the other features of adrenal hypoplasia congenita with complex glycerol kinase deficiency.