Whole exome sequencing in patients negative for MC2R, MRAP and STAR mutations, identified mutations in minichromosome maintenance 4 MCM4, nicotinamide nucleotide transhydrogenase NNT, thioredoxin reductase 2 TXNRD2, cytochrome p450scc CYP11A1, and sphingosine 1-phosphate lyase SGPL1 accounting for a further 10% of FGD.
In patients with isolated familial glucocorticoid deficiency (FGD), in which no mutations in the genes for the ACTH receptor (<i>MC2R</i>) or its accessory protein MRAP have been found, non-classic steroidogenic acute regulatory protein (<i>StAR</i>) and <i>CYP11A1</i> mutations have been described; and more recently novel mutations in genes such as nicotinamide nucleotide transhydrogenase (<i>NNT</i>) and thioredoxin reductase 2 (<i>TRXR2</i>) involved in the maintenance of the mitochondrial redox potential and generation of NADPH important for steroidogenesis and ROS detoxication have been discovered.