Category: Genetics

Professor Milewicz helps put the brakes on Thoracic Aortic Disease by linking a mutation in the gene PRKG1 to thoracic aortic dissection.

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Recently, researchers at the University of Texas Medical Branch at Galveston (UTMB) have released new information about the catastrophic rupture of the aorta known as an aortic dissection. Now, new world leading research published today in the American Journal of Human Genetics by Professor Dianna Milewicz from the University of Texas Health Science Center in Houston reveals that a mutation in the gene, PRKG1 is a major player in familial thoracic heart disease. The mutation in this gene, which encodes a protein called cGMP-dependant kinase, alters its ability to effectively regulate heart muscle cells responding to pulsating blood flow from the heart. This study is unique in that this mutation, being only one base pair out of the three billion base pairs that make up our DNA, was identified in four unrelated families of different ethnicities,.

Dr. Milewicz, whose multi-institutional team identified this mutation, commented that this mutation causes the normal functioning of this protein to become unregulated, and continually active, “almost like the brakes have failed on a car and it cannot stop!”

Knowing that this gene defect could have serious life threatening consequences provides tools to allow families to make important medical decisions following genetic testing such as aortic surveillance and elective surgery.

Every year, more than 15,000 people in the United States die when an aneurysm bursts or dissects. Aortic aneurysms are insidious because they creep up on the sufferer silently and painlessly. The blood vessel weakens without pain and ruptures can kill instantly. Research suggests that up to 20% of cases of aneurysms are hereditary and up to nine genes have already been identified that are linked to familial thoracic heart disease.

Hi Brian,

I had a dissection post-partum in 2010 and now run an interest group for those carrying the ACTA2 genetic alteration that predisposes to aortic dissection.

Your readers should know that there are predisposing genetic factors above and beyond the three obvious culprits that you listed being Marfan, ED, and LD. These newer genetic abnormalities have only been identified very recently and don’t carry any obvious external features. These people look ‘normal’ so to say. I am one of them. In my case, my dad died when I was 20 of complications following surgery for a dissected descending abdominal aorta. At the time, we did not know that he carried a faulty gene as he did not present as having Marfan Syndrome. I dissected post-partum in 2010. We pursued genetic testing and learned that I carry an abnormality named ACTA2. My dad carried it. My sister carries it. My daughter carries it.

I am learning that having a family history of aortic dissection is the MOST SIGNIFICANT risk factor for those without Marfan, LD or ED. People need to be aware of this so they can pursue testing for loved ones who may also be at risk. I wonder if you could add this as an addendum to your email so that people learn of the importance of this? If your subscribers have a dissection they NEED to tell family members to be tested genetically. The message is that even if a person does not look ‘marfanoid’ they can still carry a faulty gene that can cause a dissection.

I wonder…. have you had genetic testing yourself?

Lisa Iliadis
This should help, Brian. Let me know if you need further info/clarification. Thanks for all your work – I love your site; very valuable record… 🙂 News-MYH11 gene that is mutated

This is a very helpful post that I want to pass along:

Hi, I just wanted to update you on some things. My husband, Branden bloom has a story on your site under ascending and descending. Since he passed away I brought my kids to a pediatric heart doctor here in Sioux falls. We found that my 6 year old daughter had a PDA just like Branden did when he was 3 years old.

She had surgery on it and did great! Because of the family history of Branden’s dad and Branden and now my daughter we got sent to a genetic counselor. They got a extensive family history and decided to have 2 genes tested. Four weeks later we found the gene! It’s MYH11 gene that is mutated. Unfortunately Madyson has it. I’m so scared for her outcome down the road. With this specific gene there are only ten people in the world with this!

And my family has 3 of them! I hope this new mutilated gene they have found can become more known because right now it’s pretty new. My husbands aorta was normal in size with both dissections which through doctors off. This is why. with this gene it does not enlarge! It’s silent and very deadly. I am hoping you can let all the doctors that have been on board on your website know what we have found.

I feel this is a huge discovery in the medical field and would love to spread the word and hopefully help with research or whatever my family can do to help save my daughter life!

Thanks, Mindy Bloom.

Additional Comments:
Hi Brian,

There are many patients with defined MYH11 mutation. This often associates with PDA/Aneurysm. I have not heard about prior cases with dissection prior to significant dilatation.

I would be happy to speak with this family.



Genetics and the role they can play in determining if you are going to have an aortic dissection

FRIDAY, June 17 (HealthDay News) — Researchers have pinpointed a genetic risk factor for a potentially fatal heart problem called thoracic aortic dissection.

The life-threatening condition was the cause of the sudden death of actor John Ritter in 2003 at the age of 54.

Now, genetics researchers at the University of Texas Health Science Center at Houston and the Baylor College of Medicine found that people with duplications in DNA in a region of chromosome 16, designated 16p13.1, have a 12-fold increased risk for thoracic aortic aneurysm, an abnormal bulge caused by weakness in the wall of the aorta, the largest artery in the body. The aneurysm can lead to an aortic dissection — a usually fatal tear in the aorta.

The new findings were published June 16 in the online journal PLoS Genetics.

“The results of this study could affect clinical care because it appears patients with 16p13.1 duplications have an aggressive form of the thoracic aortic disease that causes aneurysms to dissect at smaller diameters,” the study’s senior author, Dr. Dianna Milewicz, professor and the President George H.W. Bush chair in cardiovascular research, and director of the medical genetics division at the University of Texas Medical School at Houston, said in a journal news release.

“Once doctors are able to use the entire genome, people with duplications in 16p13.1 would need to have their aortas monitored,” Milewicz said.

Each year in the United States, about 10,000 people die from thoracic aortic aneurysm and dissection, making it the 15th leading cause of death in the nation, according to background information in the news release.

While aneurysms usually have no obvious symptoms until they dissect or become very large, the U.S. National Library of Medicine states that the most common sign of aortic dissection is a sudden severe onset of chest pain described as a sharp, tearing sensation.

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