Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency

Meimaridou E., Kowalczyk J., Guasti L., Hughes C. R. , Wagner F., Frommolt P., ...More

NATURE GENETICS, vol.44, no.7, pp.740-742, 2012 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 44 Issue: 7
  • Publication Date: 2012
  • Doi Number: 10.1038/ng.2299
  • Journal Name: NATURE GENETICS
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.740-742


Using targeted exome sequencing, we identified mutations in NNT, an antioxidant defense gene, in individuals 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 reactive oxygen species (ROS) levels. Our results suggest that NNT may have a role in ROS detoxification in human adrenal glands.