Endocrine Abstracts

Mutations in CYP11A1, like those in STAR cause lipoid congenital adrenal hyperplasia manifesting with adrenal and gonadal insufficiencies along with derangements of the renin/angiotensin system. Increased adrenal size is usually a feature of STAR but not of CYP11A1 mutation. Milder forms presenting without all of these features have also been described. We present six patients from four families with CYP11A1 mutations discovered by ...

Introduction: In recent years a growing number of gene mutations have been identified which cause a myriad of syndromes having adrenal insufficiency as a core characteristic. The evolution of each syndrome is dependent on the variant and the particular gene affected. Common practice is for candidate genes to be sequenced individually, which can be time consuming and is complicated by overlapping clinical phenotypes. The increasing availability and cost effectiveness of whole e...

Aberrant pseudoexon inclusion is rarely recognised as a cause of human disease. Here we report two novel, compound heterozygous mutations in nicotinamide nucleotide transhydrogenase (NNT), one of which activates a pseudoexon, as the cause of familial glucocorticoid deficiency in two siblings. Whole-exome sequencing identified a single novel, heterozygous variant (R71X) in both affected individuals. Follow-up cDNA analysis identified the pseudoexon inclusion (p.P998_D9...

Recently, rare loss-of-function mutations of melanocortin-2-receptor accessory protein 2 (MRAP2) have been associated with severe, early-onset obesity in humans. In addition, whole body deletion and targeted brain specific deletion of the Mrap2 gene resulted in severe obesity in mice. In vitro data have shown Mrap2 interaction with the melanocortin-4-receptor (MC4R) affecting receptor signalling as a consequence. However, the mechanism by which Mrap2...