Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
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 3,300+ scientific posters on ePosters
  • More than 4,800+ 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

Uncovering a New Principle in Chemotherapy Resistance in Breast Cancer
The NIH study has revealed an entirely unexpected process for acquiring drug resistance that bypasses the need to re-establish DNA damage repair in breast cancers that have mutant BRCA1 or BRCA2 genes.
Thursday, July 21, 2016
NIH Funds Million-Person Medicine Study
NIH announces $55million in awards to build foundations for ambitious Cohort Program that aims to engage 1 million participants in lifestyle, environments and genetics research.
Friday, July 08, 2016
Largest-Ever Study of Breast Cancer Genetics in Black Women
The study will identify genetic factors that may underlie breast cancer disparities.
Thursday, July 07, 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
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
Drug Might Help Treat Sepsis
A DNA enzyme called Top1 plays a key role in turning on genes that cause inflammation in mouse and human cells in response to pathogens. A drug blocking this enzyme rescued mice from lethal inflammatory responses, suggesting a potential treatment for sepsis.
Wednesday, May 18, 2016
NIH Funds New Studies on Ethical, Legal and Social Impact of Genomic Information
Four new grants from the National Institutes of Health will support research on the ethical, legal and social questions raised by advances in genomics research and the increasing availability of genomic information.
Wednesday, May 18, 2016
Researchers Identify Genetic Links to Educational Attainment
Researchers at NIH have suggested that the large genetics analyses may be able to help discover biological pathways as well.
Thursday, May 12, 2016
Submissions Open for the Cancer Moonshot Program
NCI opens online platform to submit ideas about research for Cancer Moonshot.
Tuesday, April 19, 2016
NIH Sequences Genome of a Fungus
Researchers at the Institute have sequenced genome of human, mouse and rat Pneumocystis that cause life-threatening Pneumonia in immunosuppressed hosts.
Tuesday, April 12, 2016
Decoding Ties Between Vascular Disease, Alzheimer’s
NIH consortium uses big data, team science to uncover complex interplay of factors.
Tuesday, March 15, 2016
Researchers Find Link Between Death of Tumor-Support Cells and Cancer Metastasis
Researchers at NIH have found that the lifespan of supportive cells in a tumor may control the spread of cancer.
Tuesday, February 23, 2016
Tick Genome Reveals Secrets of a Successful Bloodsucker
NIH-funded study could lead to new tick control methods.
Tuesday, February 09, 2016
Genomic Signature Shared by Five Types of Cancer
National Institutes of Health researchers have identified a striking signature in tumor DNA that occurs in five different types of cancer.
Monday, February 08, 2016
Scientific News
Liquid Biopsies: Miracle Diagnostic or Next New Fad?
Thanks to the development of highly specific gene-amplification and sequencing technologies liquid biopsies access more biomarkers relevant to more cancers than ever before.
Colon Cancer Blocked in Mice
Case Western Reserve University Researchers block common type of colon cancer tumour in mice, laying groundwork for human clinical trial.
Discovered Through ‘Big Data’ Analysis
Researchers at the SBP have identified over 100 new genetic regions that affect the immune response to cancer.
New Therapeutic Targets For Small Cell Lung Cancer Identified
Researchers at UTSW Medical Center have identified a protein termed ASCL1 that is essential to the development of small cell lung cancer and that, when deleted in the lungs of mice, prevents the cancer from forming.
Deciphering Inactive X Chromosomes
Untangling the Barr body of inactive X chromosomes valuable for understanding chromosome structure and gene expression.
Micro Disease-Detecting Senor Created
Researchers at McMaster University have created a microscopic disease-detecting sensor that can turn on to detect trace amounts of substances.
Liquid Biopsies Treating Ovarian Cancer
Researchers have discovered a promising monitor and treat recurrence of ovarian cancer. Detecting cancer long before tumours reappear.
Uncovering a New Principle in Chemotherapy Resistance in Breast Cancer
The NIH study has revealed an entirely unexpected process for acquiring drug resistance that bypasses the need to re-establish DNA damage repair in breast cancers that have mutant BRCA1 or BRCA2 genes.
Understanding Treatment Resistant Melanoma
Researchers have determined how advanced melanoma becomes resistant; a development toward developing treatments.
Investigating ‘Black Box’ of Human Genetics
Investigations into inactive X chromosomes have shown unusual DNA repeat elements are essential for maintaining 3D structure.
Skyscraper Banner

SELECTBIO Market Reports
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
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,800+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!