Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Specific gene mutations responsible for congenital heart defects

07.07.2003


Researchers at UT Southwestern Medical Center at Dallas have discovered a gene critical to the development of the human heart and that mutations in the gene lead to congenital heart defects – the leading noninfectious cause of death in newborns.



GATA4 is only the second gene to have been identified as a cause of isolated congenital heart disease not associated with medically identified syndromes.

The findings will be published in a future edition of the journal Nature and appear online today.


The researchers identified mutations in the gene GATA4 as a cause of human cardiac septal defects, which occur when the walls separating the heart’s four chambers do not form properly.

"In terms of identifying genetic etiologies, there are not many discoveries that have been made," said Dr. Vidu Garg, assistant professor of pediatrics and one of the study’s lead authors. "This is one of the genes responsible, and we are working to identify others."

This discovery could one day help doctors prevent congenital heart defects – the most common developmental anomaly – by fixing the problem before a baby is born, said Dr. Deepak Srivastava, associate professor of pediatrics and molecular biology and the study’s senior author.

"We cannot change the fact that parents are going to pass along the mutation, but we might be able to develop a way to keep the disease from occurring," said Dr. Srivastava.

In the Nature study, researchers from UT Southwestern and three Japanese medical institutions examined two large families: one in Dallas that spanned five generations and included 16 members suffering from congenital heart defects, and a family from Tokyo spanning four generations and with eight members with congenital heart defects.

UT Southwestern researchers and Dr. Rumiko Matsuoka, a pediatric cardiologist from Japan, gathered data from the families’ medical history. Researchers also conducted physical examinations, electrocardiograms and cardiac ultrasounds. Genomic DNA from white blood cells was used for analysis, and researchers studied medical records of family members who had died.

Researchers performed a genetic linkage analysis. The analysis helps researchers find the responsible genes by comparing the genetic codes of patients suffering from heart defects with the codes of those who did not.

GATA4 mutations showed up in all family members with heart disease but not in the family members without heart disease or in 3,000 unrelated individuals.

The gene may be responsible for the defects through its interaction with TBX5, a protein that causes a subset of syndromic cardiac septal defects. Irfan Kathiriya, a student in UT Southwestern’s Medical Scientist Training Program and co-lead author, found that when a single amino of GATA4 was altered in the Dallas family, it prevented GATA4 from associating with TBX5, suggesting that the two work together to divide the heart into four chambers.

Dr. Srivastava said the next step is to determine how common GATA4 mutations are in the general population of children with heart defects and use that information to devise clever approaches to prevention. Eventually, broad screenings of individuals with congenital heart defects may help prepare them for the possibility of having a child with congenital heart defects, Dr. Garg said. The risk of that happening if either parent has a GATA4 mutation is 50 percent. In general, the risk of having a child with congenital heart disease is about 1 percent and jumps to 5 percent for parents who already have a baby with congenital heart disease.

Other UT Southwestern researchers who worked on the study were Dr. Jonathan Cohen, associate professor of internal medicine; Robert Barnes, a programmer analyst in the Eugene McDermott Center for Human Growth and Development; Marie Schluterman, a research technician in pediatrics; Dr. Isabelle King, a fellow in pediatrics; Caryn Rothrock, a biochemistry student research assistant; and Dr. Reenu Eapen, assistant professor of pediatrics. Cheryl Butler, a registered nurse at Children’s Medical Center of Dallas, also worked on the study.

Researchers from the Tokyo Women’s Medical University, the Heart Institute of Japan and Kyusyu Kosei-Nenkin Hospital in Fukuoka also took part in the study.

The study was funded by the National Institute of Child Health and Human Development; the National Heart, Lung and Blood Institute; the March of Dimes Birth Defects Foundation; Smile Train Inc.; and the Grant for the Promotion of the Advancement of Education and Research in Graduate Schools in Japan.

Staishy Bostick Siem | EurekAlert!
Further information:
http://www.swmed.edu/

More articles from Life Sciences:

nachricht More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>