Nicole Burns’ great grandfather left her his house and a portion of his 100 acres. According to a recent article in STAT News, Nicole also inherited her great grandfather’s heart disease. It was an actual hole in her heart about the size of a quarter.

It seems that the rest of her family was not spared. Almost everyone in the family was found to be affected and required heart surgery. Nicole and her sister, children, mother, aunt, and uncle underwent surgery in their teens.

Damage to the Heart

In a healthy person, blood passes through the lungs and then through the body. In some cases, either the blood is sent back to the lungs, or the holes will close entirely.

Eventually, tissue is stretched, changing the shape of the heart and its rhythm. Often a surgeon is able to patch a vein or artery. However, this procedure is often not reliable.

Nicole’s Baby Was Next

When Nicole’s baby, Cameron, was delivered by C-section his body filled with fluid, and his heart rhythm was irregular. As his condition worsened, the doctors gave Nicole two choices. They could either take Cameron off all medication and artificial support or continue to siphon the fluid and see if he will survive. Nicole chose the latter. It worked.

Cameron’s cardiologist contacted Nicole’s other cardiologist, Dr. Lo, who heads the research team. He felt that perhaps she could unravel the reason for Nicole, Cameron, and their family’s very strange heart disease.

The researchers reviewed the Burns’ family history, studying the pattern of the familial atrial septal defect; inheriting a hole in the heart.

Testing Four Generations

The researchers drove to Nicole’s farm where four generations of her family who had holes in their hearts were waiting to give blood and saliva samples to be brought back to the lab and tested.

But now that the team had the blood and saliva samples from the Burns family, they realized that the rarity of their disease presents a major problem. The team was faced with the almost impossible task of expecting to get results by testing only a few family members rather than a large number of people. Also, there are billions of places to search in the genome, so there is no quick solution to identifying their genetic variants.

Dr. Friend thought of another approach. Perhaps it would be more effective to search for a different gene. One that would correct the defect in the mysterious gene that was causing the Burns family’s heart problems.

Another researcher pointed out that many diseases have been known for years, but no drug has been developed for treatment. He explains that the problem is not finding enough genetic targets, it is the lack of drugs to treat these diseases.

The primary challenge is locating people with unidentified protective variants like the Burns family. They have no symptoms so they are obviously not going to be heading to a clinic.

The researchers believe that this is the only family in the history of researching heart defects that have this mysterious variant. Yet they still had some hope of finding a solution. It would be slow.

Years Before CRISPR

Before CRISPR gene editing, it was expensive to sequence whole genomes. The researchers had to read short pieces of DNA then attempt to piece together the code containing instructions to make proteins.

The team was searching for a mutation that would explain the heart problems but found nothing. Years passed and Nicole’s doctors still had no news. Then her mother and aunt both died due to heart attacks.

Five years later, the sequencing process became so much less expensive that the doctors retrieved the family’s vials of samples. Now if they found mutations, using CRISPR gene-editing tools, they were able to insert them into mice quickly.

The researchers took pieces of DNA from Burns family members and inserted them chemically into the heart muscle cells of mice. They could see that even with a structural defect, the cells could generate a pulse.

But there were still unanswered questions. How had the two mutations caused the unique symptoms in the Burns family? And why the heart holes? The first gene was known to be important in heart tissue growth. But the question is why would the pair cause heart holes?

The team had to accept the fact that before they can even think about therapy, they need to know exactly what is causing the problem. Therefore, they knew any treatment development was far into the future.

Dr. Lo wanted to keep Nicole in a positive frame of mind and told her that she is really blessed. She said that no one in four Burns generations would have been born if they did not have this “mysterious” mutation. Of course, Nicole was worried about her own children as she believed that the symptoms had been getting more severe with each new generation.

Nicole remembers how sick Cameron was at birth, and that he needed surgery to repair the holes in his heart when he was a baby. Years later he was hospitalized for heart failure once more. She witnessed stillbirths and miscarriages in her family.

In Conclusion

Nicole was relieved to hear that for the moment her case was closed. The family would still be monitored by cardiologists, but there would not be any answers for a long time.