Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

NIH Researchers Identify Mutation Linked to Severe Form of Cushing’s Syndrome

Published: Friday, February 28, 2014
Last Updated: Friday, February 28, 2014
Bookmark and Share
Mutation in related gene found in patient with Carney Complex.

Mutations in a gene containing part of the information needed to make an enzyme that provides energy for governing basic cell functions appear to contribute to a severe form of Cushing’s syndrome, according to researchers at the National Institutes of Health and nine European research institutions.

Cushing’s syndrome ( results when the body is exposed to too much of the stress hormone cortisol. The syndrome may result when the body itself produces excess cortisol, causing symptoms that may include high blood pressure, muscle weakness or osteoporosis.

The study was published online in the New England Journal of Medicine. In a letter to the editor of the same journal, members of the NIH research team and researchers in Italy reported that a mutation in another gene containing information needed to make yet another portion of the enzyme appears to be central to Carney Complex (, a rare disease that causes multiple tumors and which is characterized by increased cortisone levels.

For the study on Cushing’s syndrome, the researchers examined tissue from patients having a subtype of Cushing’s syndrome, in which the source of the excess cortisol is a noncancerous tumor confined to only one of the body’ two adrenal glands. The researcher examined samples from nearly 200 such adrenal gland tumors. They found that 37 percent contained a mutation in the gene known as PRKACA.

“The mutation we identified appears to give rise to one of the most common kinds of adrenal tumors seen in Cushing’s syndrome,” said study co- first author Constantine Stratakis, M.D., D.Sc., director of the Division of Intramural Research and head of the Program on Developmental Endocrinology and Genetics at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the NIH institute that took part in the study. “The discovery suggests a clear path forward for investigating medications that might block the production of excess cortisol.”

The PRKACA gene contains the information needed to make a portion, or subunit, of the PKA (protein kinase A) enzyme. The enzyme is involved in numerous chemical reactions in the cell.

For these patients, the mutant PRKACA gene was found only in the tumor cells, and not in other cells of the body. Because the gene was not found in other cells of the body, the mutation likely arose spontaneously in the adrenal tissue.

The researchers also examined tissue from patients who had non-cancerous growths on both adrenal glands. In samples from these patients, the researchers found an extra copy of the PRKACA gene. This extra copy, they noted, was present in all of the patients’ cells, and was not limited to the tumor tissue. Because the mutation was found in all the cells of the body, it was likely hereditary.

However, in both the cases involving the spontaneous mutation and the inherited mutation, the activity of the PKA enzyme was increased.

“The mutation appears to spur the activity of this enzyme, Dr. Stratakis said. “The result appears to be an increase in cell growth and division in adrenal tissue, and an overproduction of cortisol.”

Dr. Stratakis collaborated with the other co-first authors, including Felix Beuschlein, M.D., of the Ludwig-Maximilians-University, in Munich, Germany; Martin Fassnacht, M.D., of Ludwig-Maximilians-University and the University of Wurtzburg, in Wurtzburg, Germany; Guillaume Assie, M.D., Ph.D., of the Paris Descartes University and Cochin Hospital, in Paris; Davide Calebiro, M.D., of the University of Wurtzburg; and 25 other researchers at the NICHD and institutions in France, Germany and Italy.

In a letter to the editor of the same issue of the New England Journal of Medicine, Orsetta Zuffardi of the University of Pavia, in Pavia, Italy and Dr. Stratakis and other colleagues in Italy and at the NIH discovered that a patient with Carney Complex, who had a tumor in the pituitary gland and elevated growth hormone, had an extra copy of the PRKACB gene. This gene codes for another subunit of Protein Kinase A. In addition to elevated growth hormone levels, people with Carney Complex often have skin spots and increased risk of tumors in the pituitary, adrenals as well as other parts of the body.

“It’s likely that the extra copy of this gene also increases the activity of protein kinase A, essentially setting the stage for increased cell proliferation and higher production of hormones,” Dr. Stratakis said.

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More Than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Lucentis Effective for Proliferative Diabetic Retinopathy
NIH-funded clinical trial marks first major advance in therapy in 40 years.
Tuesday, November 24, 2015
Batten Disease may Benefit from Gene Therapy
NIH-funded animal study suggests one-shot approach to injecting genes.
Friday, November 13, 2015
Molecule Proves Key to Brain Repair After Stroke
Scientists found that a molecule known as growth and differentiation factor 10 (GDF10) plays a key role in repair mechanisms following stroke.
Tuesday, November 10, 2015
NIH Researchers Link Single Gene Variation to Obesity
Variation in the BDNF gene may affect brain’s regulation of appetite, study suggests.
Saturday, October 31, 2015
Researchers Identify Potential Alternative to CRISPR-Cas Genome Editing Tools
New Cas enzymes shed light on evolution of CRISPR-Cas systems.
Saturday, October 31, 2015
Potential Alternative to CRISPR-Cas Genome Editing Tools
New Cas enzymes shed light on evolution of CRISPR-Cas systems.
Friday, October 23, 2015
Charting Genetic Variation Across the Globe
An international team of scientists has created the world’s largest catalog of human genetic differences in populations around the globe.
Tuesday, October 20, 2015
Gene Therapy Staves Off Blindness from Retinitis Pigmentosa in Canine Model
NIH-funded study suggests therapeutic window may extend to later-stage disease.
Tuesday, October 20, 2015
Nuclear Transport Problems Linked to ALS and FTD
NIH-supported studies point to potential new target for treating neurodegenerative diseases.
Monday, October 19, 2015
Scientists Develop Genetic Blueprint of Inner Ear Cell Development
Two studies in mice use new technique to provide insight into cell development critical for hearing, balance.
Saturday, October 17, 2015
$21M Invested in Research Hubs in Developing Countries
The National Institutes of Health and other U.S. and Canadian partners are investing $20.9 million dollars over five years to establish seven regional research and training centers in low- and middle-income countries (LMICs).
Friday, October 09, 2015
NIH Breast Cancer Research to Focus On Prevention
A new phase of the Breast Cancer and the Environment Research Program (BCERP), focused on prevention, is being launched at the National Institutes of Health.
Friday, October 09, 2015
NIH Grantees Win 2015 Nobel Prize in Chemistry
The 2015 Nobel Prize in chemistry has been awarded to NIH grantees Paul Modrich, Ph.D., of the Howard Hughes Medical Institute and the Duke University School of Medicine, Durham, N.C.; and Aziz Sancar, M.D., Ph.D., of the University of North Carolina, Chapel Hill, N.C.,.
Thursday, October 08, 2015
NIH Announces High-Risk, High-Reward Research Awardees
NIH to fund 78 awards to support highly innovative biomedical research.
Wednesday, October 07, 2015
New Gene Therapy for Vision Loss From a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Tuesday, October 06, 2015
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
The MaxSignal Colistin ELISA Test Kit from Bioo Scientific
Kit can help prevent the antibiotic apocalypse by keeping last resort drugs out of the food supply.
"Good" Mozzie Virus Might Hold Key to Fighting Human Disease
Australian scientists have discovered a new virus carried by one of the country’s most common pest mosquitoes.
Non-Disease Proteins Kill Brain Cells
Scientists at the forefront of cutting-edge research into neurodegenerative diseases such as Alzheimer’s and Parkinson’s have shown that the mere presence of protein aggregates may be as important as their form and identity in inducing cell death in brain tissue.
Closing the Loop on an HIV Escape Mechanism
Research team finds that protein motions regulate virus infectivity.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Potential Treatment for Life-Threatening Viral Infections Revealed
The findings point to new therapies for Dengue, West Nile and Ebola.
World’s First Therapeutic Venom Database
Open-source library describes nearly 43,000 effects on the human body.
Biologists Induce Flatworms to Grow Heads and Brains of Other Species
Findings shed light on role of a new kind of epigenetic signaling in evolution, could yield clues for understanding birth defects and regeneration.
Fat Cells Originating from Bone Marrow Found in Humans
Cells could contribute to diabetes, heart disease.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos