Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mutations in HRAS gene sequence confirmed in patients with Costello syndrome

05.12.2005


The mutation was not found in patients’ parents’ DNA



Gene mutations in the HRAS sequence are present in most patients affected with Costello syndrome, according to a new study in the American Journal of Medical Genetics. The mutations occurred de novo in patients, meaning, they were not observed in their parents’ genes. The study is published in the December issue of the journal, which is published by John Wiley & Sons. It is also available online via Wiley Interscience.

Costello Syndrome is very rare, with only 150 cases reported worldwide. It is associated with mental retardation, distinctive facial characteristics, cardiovascular abnormalities, and a predisposition for tumors. Patients often develop soft tissue tumors in childhood and bladder cancer as young adults.


A previous genetic study of 12 Japanese and Italian patients with Costello syndrome found mutations in the HRAS gene sequence. To confirm this connection and expand the understanding of the possible cause of Costello syndrome, researchers, led by Karen W. Gripp of A. I. DuPont Hospital for Children in Wilmington, Delaware, performed mutation analyses on 40 North American and European patients.

The researchers identified patients with the syndrome through affiliated organizations and physician referral. They extracted DNA from blood, saliva or cell lines and performed DNA sequencing. When possible, they also sequenced the genes of the patients’ parents.

The results were striking. Among the patients with Costello syndrome, "We detected missense mutations in HRAS in 33 (82.5%) patients," the authors report. "All mutations affected either codon 12 or 13 of the protein product, with G12S occurring in 30 (90.9%) patients of the mutation-positive cases."

The researchers reviewed the clinical presentation of the patients who did not have HRAS mutation and found inconsistencies in their facial characteristics. They suggest that these patients may not have Costello syndrome, but rather cardio-facio-cutaneous syndrome. Lack of an identifiable HRAS mutation should not yet exclude the diagnosis of Costello syndrome, however, the results of this study should allow doctors to confirm a clinical diagnosis of Costello syndrome.

Of the 19 sets of parents tested, none carried the sequence change found in their children, indicating that the mutation occurred in the parents’ germ cells. The nature of the missense mutations, along with the paternal age effect observed in Costello syndrome suggests a paternal origin of the mutations, the researchers report.

"Five different HRAS mutations have now been reported in Costello syndrome, however genotype-phenotype correlation remains incomplete," the authors conclude. And while it is too early to apply their findings to the recommendations for clinical care, they hope to collect additional data to achieve this goal.

Offering hope to those affected by the syndrome, they conclude, "The identification of these mutations in combination with the knowledge from cancer research on HRAS and the MAPK pathway will allow for the use of medications directed at this pathway."

Amy Molnar | EurekAlert!
Further information:
http://www.interscience.wiley.com

More articles from Life Sciences:

nachricht Nonstop Tranport of Cargo in Nanomachines
20.11.2018 | Max-Planck-Institut für molekulare Zellbiologie und Genetik

nachricht Researchers find social cultures in chimpanzees
20.11.2018 | Universität Leipzig

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Nonstop Tranport of Cargo in Nanomachines

Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.

Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Optical Coherence Tomography: German-Japanese Research Alliance hosted Medical Imaging Conference

19.11.2018 | Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

 
Latest News

Nonstop Tranport of Cargo in Nanomachines

20.11.2018 | Life Sciences

Researchers find social cultures in chimpanzees

20.11.2018 | Life Sciences

When AI and optoelectronics meet: Researchers take control of light properties

20.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>