Navigation Links
Closing in on Lethal Heart Rhythm in Young Athletes

Johns Hopkins experts on the genetics of a potentially lethal heart rhythm defect that runs in families and targets young athletes report they have greatly narrowed //the hunt for the specific genetic mutations that contribute to the problem.

Their new findings, described in the July issue of the American Journal of Human Genetics, should increase the accuracy of tests to identify those at risk for arrhythmogenic right ventricular dysplasia (ARVD), which is among the top causes of sudden cardiac death in the young and fit.

In February, the same team linked one-third of ARVD cases in their large database of patients to a dozen abnormal changes in a gene called plakophilin-2 (PKP2), which makes proteins involved in heart cell stickiness.

In the new study, confirming experiments elsewhere, the Hopkins team found four mutations in another sticky protein gene, Desmoglein-2 (DSG2), in five of 33 patients tested.

“This gene is highly expressed in the heart, where muscle tissue expands and contracts with the heartbeat,” says senior study author and cardiac geneticist Daniel P. Judge, M.D. “Our results confirm that altered genes in the desmosomal cellular complex are responsible for ARVD. And now that we know the genetic roots of this disease, we can also create better blood tests for their proteins to predict who is at risk for developing this condition.”

ARVD is characterized by weakness in the desmosome, or cell-to-cell binding structure. The inherited condition leads to the buildup of excess fatty and scar tissue in the heart’s right ventricle, causing irregular beats and - unless diagnosed and treated with drugs or implanted defibrillators - triggering a fatal heart rhythm disturbance.

Judge, an assistant professor at The Johns Hopkins University School of Medicine and its Heart Institute, says DSG2 mutations appear to account for at least 10 percent and possibly more of the estimated 25,000 deaths each year from ARVD.

'We expect a test for DSG2 mutations to be available to those with a family history of the condition before the end of the year,' he says. The same Hopkins team developed a blood test to screen for PKP2 mutations. That test became available in May and is currently the only one available for detecting those at greater risk of the disease.

More than 400 people have been screened at Hopkins so far and of these, two-thirds have had serious enough forms of the condition to warrant implantation of a defibrillator, an electrical device that corrects any disturbances in the heart's rhythm.

The Hopkins researchers identified the DSG2 mutation through genetic analysis of blood taken from 60 men and women already diagnosed with ARVD. All were part of a patient database created at Hopkins in 1998. The researchers focused on cell-adhesion proteins because they had already been linked to Naxos syndrome, which produced symptoms in the right ventricle similar to those documented in ARVD.

When scientists excluded their ARVD patients with PKP2 mutations, they were left with 33 who had no known genetic explanation for their condition. Additional testing revealed the four mutations in DSG2.

'We knew right away that we had found something very significant,' says lead author Mark Awad, B.A., a medical and predoctoral sciences student at Hopkins. 'The mutations were confined to a highly functional part of the gene and were highly conserved, meaning that evolution had not drastically changed the genetic sequence over time - the gene was kept the way it was because it was important to the heart’s normal function.'

According to Awad, not everyone with a genetic mutation develops ARVD. He adds that further analysis of the condition’s genetic roots will help researchers to calculate the precise increased risk from each mutation for developing symptoms and dying. Previous research by the Hopkins team sh owed that familial ARVD generally strikes after puberty and its symptoms - dizziness, fatigue and fainting after exercise - may appear up to 15 years before diagnosis.


Related medicine news :

1. Closing In On the Breast Cancer Gene
2. Brain Networks Strengthened by Closing Ion Channels
3. Lethal Heart Condition linked To Cocaine Use
4. Toll-like Receptor (Tlr3) Attachment Leads To Lethal Encephalitis
5. How Lethal Is The H5N1?
6. Whirlpool Bath Tubs Contain Potentially Lethal Bacterial Strains
7. Mineral Water Stored In Plastic Containers For Long Could Be Lethal
8. Echocardiography-Guided Genetic Test Could Improve Screening For Lethal Heart Condition
9. Elements In Grape fruit Juice Combine Lethally with Certain Drugs, leading to potentially dangerous side effects, study.
10. Warning! Working For Long Hours On Your Computer Can Be Lethal
11. "Serious Failings" Led To Spread Of Lethal Hospital Bug
Post Your Comments:

(Date:6/27/2016)... ... 2016 , ... "FCPX editors can now reveal their media with growing colorful ... Christina Austin - CEO of Pixel Film Studios. , ProSlice Color brings the ... can now reveal the media of their split screens with growing colorful panels. , ...
(Date:6/26/2016)... ... 2016 , ... Quality metrics are proliferating in cancer care, and are derived ... eye of the beholder, according to experts who offered insights and commentary in the ... Care. For the full issue, click here . , For the American Society ...
(Date:6/26/2016)... , ... June 26, 2016 , ... ... once they have been diagnosed with endometriosis. These women need a treatment plan ... require a comprehensive approach that can help for preservation of fertility and ultimately ...
(Date:6/25/2016)... (PRWEB) , ... June 25, 2016 , ... First ... United States, named Dr. Sesan Ogunleye, as the Medical Director of its new Mesquite-Samuell ... facility Medical Director of our new Mesquite location,” said Dr. James M. Muzzarelli, Executive ...
(Date:6/24/2016)... ... June 24, 2016 , ... A recent article published June 14 ... The article goes on to state that individuals are now more comfortable seeking to ... operations such as calf and cheek reduction. The Los Angeles area medical group, Beverly ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... HOUSTON , June 23, 2016  MedSource ... platform as its e-clinical software solution of choice.  ... the best possible value to their clients by ... nowEDC.  The preferred relationship establishes nowEDC as the ... pricing for MedSource,s full-service clients.  "nowEDC has long ...
(Date:6/23/2016)... 23, 2016 Any dentist who has made an ... current process. Many of them do not even offer this ... and high laboratory costs involved. And those who ARE able ... such a high cost that the majority of today,s patients ... Parsa Zadeh , founder of Dental Evolutions Inc. and ...
(Date:6/23/2016)... a startling report released today, National Safety Council research ... proven plan to eliminate prescription opioid overdoses. Prescription Nation ... tackling the worst drug crisis in recorded U.S. history, assigned a ... , New Mexico , Tennessee ... failing states, three – Michigan , ...
Breaking Medicine Technology: