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Gene mutation may lead to development of adrenal Cushing's syndrome

Published online 25 April 2014

Aisha El-Awady

A gene mutation may play a role in the development of adrenal Cushing's syndrome, a metabolic disorder caused by prolonged exposure of the body to high levels of the hormone cortisol.

The hormone, produced in excess by adrenal gland tumours or adrenal hyperplasia, triggers a condition in which adrenal gland cells proliferate abnormally. Symptoms include rapid weight gain, diabetes and hypertension.

Using whole-exome and RNA sequencing, an international team of researchers, led by Guang Ning and Weiqing Wang from Shanghai Jiao Tong University School of Medicine in China and Jun Wang from the University of Hong Kong and the King Abdulaziz University, Jeddah, Saudi Arabia, discovered that 69.2% of patients with adrenocortical adenomas showed an activating mutation in a certain area of the PRKACA gene.

Patients with the mutation showed an increase in the activity of protein kinase C, which modifies proteins by chemically adding phosphate groups to them. This process, known as phosphorylation, leads to a change in the target protein's activity level.

The team also found recurrent mutations in the DOT1L gene in patients with adrenocorticotropic hormone-independent macronodular adrenocortical hyperplasia and in the CLASP2 gene in those with adrenocortical oncocytoma.

The researchers hope their findings, published in the journal Science on April 3 2014, may serve as a guide for future studies on the prevention or treatment of Cushing's syndrome.


  1. Cao, Y. et al. Activating Hotspot L205R Mutation in PRKACA and Adrenal Cushing’s Syndrome. Science (2014) doi:10.1126/science.1249480