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 When predictions of theoretical chemists become reality
22.05.2020 | Technische Universität Dresden

nachricht From artificial meat to fine-tuning photosynthesis: Food System Innovation – and how to get there
20.05.2020 | Potsdam-Institut für Klimafolgenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: I-call - When microimplants communicate with each other / Innovation driver digitization - "Smart Health“

Microelectronics as a key technology enables numerous innovations in the field of intelligent medical technology. The Fraunhofer Institute for Biomedical Engineering IBMT coordinates the BMBF cooperative project "I-call" realizing the first electronic system for ultrasound-based, safe and interference-resistant data transmission between implants in the human body.

When microelectronic systems are used for medical applications, they have to meet high requirements in terms of biocompatibility, reliability, energy...

Im Focus: When predictions of theoretical chemists become reality

Thomas Heine, Professor of Theoretical Chemistry at TU Dresden, together with his team, first predicted a topological 2D polymer in 2019. Only one year later, an international team led by Italian researchers was able to synthesize these materials and experimentally prove their topological properties. For the renowned journal Nature Materials, this was the occasion to invite Thomas Heine to a News and Views article, which was published this week. Under the title "Making 2D Topological Polymers a reality" Prof. Heine describes how his theory became a reality.

Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other...

Im Focus: Rolling into the deep

Scientists took a leukocyte as the blueprint and developed a microrobot that has the size, shape and moving capabilities of a white blood cell. Simulating a blood vessel in a laboratory setting, they succeeded in magnetically navigating the ball-shaped microroller through this dynamic and dense environment. The drug-delivery vehicle withstood the simulated blood flow, pushing the developments in targeted drug delivery a step further: inside the body, there is no better access route to all tissues and organs than the circulatory system. A robot that could actually travel through this finely woven web would revolutionize the minimally-invasive treatment of illnesses.

A team of scientists from the Max Planck Institute for Intelligent Systems (MPI-IS) in Stuttgart invented a tiny microrobot that resembles a white blood cell...

Im Focus: NASA's Curiosity rover finds clues to chilly ancient Mars buried in rocks

By studying the chemical elements on Mars today -- including carbon and oxygen -- scientists can work backwards to piece together the history of a planet that once had the conditions necessary to support life.

Weaving this story, element by element, from roughly 140 million miles (225 million kilometers) away is a painstaking process. But scientists aren't the type...

Im Focus: Making quantum 'waves' in ultrathin materials

Study co-led by Berkeley Lab reveals how wavelike plasmons could power up a new class of sensing and photochemical technologies at the nanoscale

Wavelike, collective oscillations of electrons known as "plasmons" are very important for determining the optical and electronic properties of metals.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

International Coral Reef Symposium in Bremen Postponed by a Year

06.04.2020 | Event News

 
Latest News

New technology can detect anti-virus antibody in 20 minutes

25.05.2020 | Medical Engineering

ATLAS telescope discovers first-of-its-kind asteroid

25.05.2020 | Physics and Astronomy

Researchers develop high-performance cancer vaccine using novel microcapsules

25.05.2020 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>