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

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 (http://www.nichd.nih.gov/health/topics/cushing/Pages/default.aspx) 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 (http://ghr.nlm.nih.gov/condition/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

Join For Free

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 3,200+ scientific posters on ePosters
  • More Than 4,700+ 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 TechnologyNetworks.com 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

Implementation Science Approaches to Reduce Mother-to-Child HIV Transmission
The NIH study will investigate best practices to ease major disease burden in Sub-Saharan Africa.
Friday, July 01, 2016
Significant Expansion Of Data Available In The Genomic Data Commons
Cancer genomic profile information from 18,000 adult cancer patients will be added to the database.
Wednesday, June 29, 2016
Some Women With PCOS May Have Adrenal Disorder
Researchers at NIH have found that a subgroup of women with PCOS, a leading cause of infertility, may produce excess adrenal hormones.
Tuesday, June 28, 2016
Manufactured Stem Cells To Advance Clinical Research
Clinical-grade cell line will enable development of new therapies and accelerate early-stage clinical research.
Tuesday, June 28, 2016
Rates of Nonmedical Prescription Opioid Use Disorder Double in 10 Years
Researchers at NIH have found that the nonmedical use of prescription opioids has more than doubled among adults in the United States from 2001-2002 to 2012-2013.
Thursday, June 23, 2016
Peanut Allergy Prevention Strategy is Nutritionally Safe
Early-life peanut consumption does not affect duration of breastfeeding or children’s growth and nutrition.
Wednesday, June 22, 2016
NIH Launches Large Study of Pregnant Women in Areas Affected by Zika virus
Researchers at NIH and Fiocruz have begun a study to evaluate the magnitude of health risks that Zika virus infection poses to pregnant women and their developing fetuses and infants.
Wednesday, June 22, 2016
New Imaging Method May Predict Risk of Post-Treatment Brain Bleeding After Stroke
Researchers at NIH have developed technique that provides new insight into stroke.
Tuesday, June 21, 2016
Study Reveals Central Role of Endocannabinoids in Habit Formation
The new study findings point to a previously unknown mechanism in the brain that regulates the transition between goal-directed and habitual behaviors.
Tuesday, June 21, 2016
Predicting Effective Drug Combinations For TB
Researchers analyzed gene regulatory networks to explain the effectiveness of an experimental drug combination against drug-resistant tuberculosis bacteria.
Wednesday, June 15, 2016
Genomic Data Commons Launched
Part of the National Cancer Moonshot, the GDC will centralize and standardize accessible data.
Tuesday, June 07, 2016
Prevention May be Essential to Reducing Racial Disparities in Stroke
Researchers at NIH have found study provides clues to differences in stroke deaths between blacks and whites.
Friday, June 03, 2016
NIH Funds Biobank To Support Precision Medicine Initiative Cohort Program
$142 million over five years will be awarded to the Mayo Clinic to establish the world’s largest research-cohort biobank for the PMI Cohort Program
Friday, May 27, 2016
Advancing Protein Visualization
Cryo-EM methods can determine structures of small proteins bound to potential drug candidates.
Friday, May 27, 2016
New NIH-EPA Research Centers to Study Environmental Health Disparities
Scientists will partner with community organizations to study these concerns and develop culturally appropriate ways to reduce exposure to harmful environmental conditions.
Thursday, May 26, 2016
Scientific News
Open Source Seed Initiative – A Welcome Boost to Global Crop Breeding
A team of plant breeders, farmers, non-profit agencies, seed advocates, and policymakers have created the Open Source Seed Initiative.
ASMS 2016: Targeting Mass Spectrometry Tools for the Masses
The expanding application range of MS in life sciences, food, energy, and health sciences research was highlighted at this year's ASMS meeting in San Antonio, Texas.
Implementation Science Approaches to Reduce Mother-to-Child HIV Transmission
The NIH study will investigate best practices to ease major disease burden in Sub-Saharan Africa.
Tough New Hydrogel Hybrid Doesn’t Dry Out
Water-based material could be used to make artificial skin, longer-lasting contact lenses.
New CAR T Cell Therapy Using Double Target Aimed at Solid Tumors
Researchers at Penn University have described how antibody, carbohydrate combination could apply to range of cancer types.
Lasers Carve the Path to Tissue Engineering
A new technique, developed at EPFL, combines microfluidics and lasers to guide cells in 3D space, overcoming major limitations to tissue engineering.
Link Between Canned Food, BPA Exposure Revealed
New Stanford research resolves the debate on the link between canned food and exposure to the hormone-disrupting chemical known as Bisphenol A, or BPA.
Portable Test Rapidly Detects Zika
To better diagnose and track the disease, scientists are now reporting a new $2 test that in the lab can accurately detect low levels of the virus in saliva.
Erasing Unpleasant Memories with a Genetic Switch
Researchers from KU Leuven and the Leibniz Institute for Neurobiology have managed to erase unpleasant memories in mice using a 'genetic switch'.
Unidentified Spectra Detector
New algorithm clusters over 250 million spectra for analysis, such that millions of unidentified peptide sequences can be recognised.
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
3,200+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!