Mutations in gigantic gene responsible for common heart muscle disease
2012-02-16
(Press-News.org) BOSTON, MA—Mutations in TTN—the largest gene in the human genome—cause idiopathic (unknown cause) dilated cardiomyopathy (DCM), a common form of heart failure, according to a study by Brigham and Women's Hospital (BWH) researchers. The TTN gene encodes a protein that functions as a scaffold for assembly of contractile proteins in muscle cells and also regulates the production of force in cardiac muscle cells.
Because of its enormous size, the TTN gene was, until recently, too difficult to sequence and analyze in large numbers of patients. But with the development of next-generation sequencing technologies, the time was ripe to tackle TTN. Christine Seidman, MD, BWH Cardiovascular Genetics Center director and a team of dedicated scientists at Harvard Medical School; Imperial College, London; University of Colorado; and physicians at BWH took on the challenge to comb through the gigantic gene. Their study unveils how mutated TTN genes can lead to structural deformations in heart muscle fibers, which may then lead to heart muscle disease. The study will be published in the February 16, 2012 issue of The New England Journal of Medicine.
Researchers analyzed genetic samples from 312 people diagnosed with DCM, 231 with another heart muscle disease called hypertrophic cardiomyopathy (HCM), and 249 people without heart disease. They identified 72 mutations in the TTN gene that foreshorten the encoded protein. These shortened titin proteins lack regions involved in regulating force production in heart cells. Many more mutations were found in those with DCM compared to healthy individuals and those with HCM, indicating that TTN gene mutation causes DCM, but rarely causes HCM.
Moreover, the study notes that outcomes of patients with DCM were similar regardless of whether or not a person has a TTN gene mutation. However, among those that did have TTN mutations, adverse events such as cardiac transplantation, implantation of a ventricular assist device, or death occurred earlier in men than women. Seidman believes that the study findings will help improve future diagnosis and treatment of heart diseases.
"Early diagnosis of any disease, including DCM, can allow interventions that may prevent some of the devastating outcomes, such as sudden cardiac death from an arrhythmia or development of heart failure," said Seidman. "By knowing that TTN mutations account for a substantial amount of idiopathic DCM, we now will have the opportunity for early diagnosis in lots of at-risk individuals, and any person who has a family member with idiopathic DCM."
###
This research was supported by funding from Howard Hughes Medical Institute; National Institutes of Health Leducq Foundation; American Heart Association and Muscular Dystrophy Association; UK National Institute for Health Research Cardiovascular Biomedical Research Unit (Royal Brompton and Harefield NHS Foundation Trust & Imperial College), The British Heart Foundation and the MRC UK; and J. Ira and Nicki Harris Family Research Award.
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare, an integrated health care delivery network. BWH is the home of the Carl J. and Ruth Shapiro Cardiovascular Center, the most advanced center of its kind. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives and its dedication to educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), www.brighamandwomens.org/research, BWH is an international leader in basic, clinical and translational research on human diseases, involving more than 900 physician-investigators and renowned biomedical scientists and faculty supported by more than $537 M in funding. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative. For more information about BWH, please visit www.brighamandwomens.org.
END
ELSE PRESS RELEASES FROM THIS DATE:
2012-02-16
A medication commonly used to help people stop smoking may have an unanticipated positive side effect for an entirely different vice: drinking alcohol. A new study by University of Chicago researchers finds that varenicline, sold as Chantix, increases the negative effects of alcohol and therefore could hold promise as a treatment for alcoholism.
A group of heavy-to-moderate social drinkers given a single dose varenicline three hours before an alcoholic beverage reported increased dysphoria and reduced "liking," even when researchers controlled for the effects of nausea ...
2012-02-16
A team led by a University of British Columbia professor has developed a new class of drugs that completely suppress absence seizures – a brief, sudden loss of consciousness – in rats, and which are now being tested in humans.
Absence seizures, also known as "petit mal seizures," are a symptom of epilepsy, most commonly experienced by children. During such episodes, the person looks awake but dazed. The seizures, arising from a flurry of high-frequency signals put out by the neurons of the thalamus, can be dangerous if they occur while a person is swimming or driving, ...
2012-02-16
The ability to change vocal sounds (vocal plasticity) and develop an accent is potentially far more widespread in mammals than previously believed, according to new research on goats from Queen Mary, University of London.
Vocal plasticity is the ability of an individual to modify the sound of their voice according to their social environment. Humans benefit from an extreme form of vocal plasticity which allows us to produce a wide range of sounds and accents, but in most other mammals (except, for example, bats and whales) vocalisations were thought to be genetically ...
2012-02-16
The study of more than 11,000 pregnant women, in partnership with Mars Petcare, showed that those who owned dogs were approximately 50% more likely to achieve the recommended 30 minutes of exercise a day through high levels of brisk walking than those without dogs. Scientists suggest that as it is a low-risk exercise, walking a dog could form part of a broader strategy to improve the health of pregnant women.
Previous studies have shown that maternal obesity and large weight gain during pregnancy has adverse outcomes for mother and child. Studies show, for example, that ...
2012-02-16
CINCINNATI -- As part of the first national, randomized clinical trial to study two methods of drug delivery for seizing patients, researchers have shown that using an auto-injector, similar to an EpiPen, to deliver anticonvulsant medication stops prolonged seizures more quickly and effectively than drug delivery through an IV line.
The research, which will be published in the Feb. 16 edition of the New England Journal of Medicine, was conducted as part of the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), which included University of Cincinnati (UC) ...
2012-02-16
VTT Technical Research Centre of Finland, the leading multi-technological applied research organisation in Northern Europe, has developed an optical accessory that turns an ordinary camera phone into a high-resolution microscope. The device is accurate to one hundredth of a millimetre. Among those who will benefit from the device are the printing industry, consumers, the security business, and even health care professionals. A new Finnish enterprise called KeepLoop Oy and VTT are already exploring the commercial potential of the invention. The first industrial applications ...
2012-02-16
BOSTON, MA (February 15, 2012) — For decades, researchers have sought a genetic explanation for idiopathic dilated cardiomyopathy (DCM), a weakening and enlargement of the heart that puts an estimated 1.6 million Americans at risk of heart failure each year. Because idiopathic DCM occurs as a familial disorder, researchers have long searched for genetic causes, but for most patients the etiology for their heart disease remained unknown.
Now, new work from the lab of Christine Seidman, a Howard Hughes Investigator and the Thomas W. Smith Professor of Medicine and Genetics ...
2012-02-16
When a person is experiencing a prolonged convulsive seizure, quick medical intervention is critical. With every passing minute, the seizure becomes harder to stop, and can place the patient at risk of brain damage and death. This is why paramedics are trained to administer anticonvulsive medications as soon as possible -- traditionally giving them intravenously before arriving at the hospital.
Now a major clinical trial has shown that an even faster method that involves injecting the drugs into the thigh muscle using an autoinjector (similar to a pre-loaded syringe) ...
2012-02-16
Like a stream of air shooting out of an airplane's broken window to relieve cabin pressure, scientists at Scripps Institution of Oceanography at UC San Diego say lava formations in eastern Oregon are the result of an outpouring of magma forced out of a breach in a massive slab of Earth. Their new mechanism explaining how such a large volume of magma was generated is published in the Feb. 16 issue of the journal Nature.
For years scientists who study the processes underlying the planet's shifting tectonic plates and how they shape the planet have debated the origins of ...
2012-02-16
Astronomers using NASA's Hubble Space Telescope have found a cluster of young, blue stars encircling the first intermediate-mass black hole ever discovered. The presence of the star cluster suggests that the black hole was once at the core of a now-disintegrated dwarf galaxy. The discovery of the black hole and the star cluster has important implications for understanding the evolution of supermassive black holes and galaxies.
"For the first time, we have evidence on the environment, and thus the origin, of this middle-weight black hole," said Mathieu Servillat, who worked ...
LAST 30 PRESS RELEASES:
[Press-News.org] Mutations in gigantic gene responsible for common heart muscle disease
