Mutations in Nicotinamide Nucleotide Transhydrogenase (NNT) cause familial glucocorticoid deficiency

Using targeted exome sequencing we identified mutations in NNT, an antioxidant defence gene, in patients with familial glucocorticoid deficiency. In mice with Nnt loss, higher levels of adrenocortical cell apoptosis and impaired glucocorticoid production were observed. NNT knockdown in a human adrenocortical cell line resulted in impaired redox potential and increased ROS levels. Our results suggest that NNT may have a role in ROS detoxification in human adrenal glands.