Researchers at Thomas Jefferson University in Philadelphia found that mutations to the gene JUP, known to underlie skin conditions such as epidermolysis bullosa (EB), can also lead to serious heart disease.
Findings of the study published online ahead of print in the journal Scientific Reports (Dec. 10, 2020), suggest that skin specialists could be in a position to diagnose systemic disease early.
“By looking into the skin of newborns, we can predict the development of a devastating heart disease later in life,” said Dr. Jouni Uitto, in a press release. Dr. Uitto is a Professor of Dermatology and Cutaneous Biology at Thomas Jefferson University. “This is predictive personalized medicine at its best.”
For the study researchers investigated the DNA of more than 360 EB patients from around the world. The study’s authors analyzed DNA isolated from blood samples for sequence variants in a set of 21 genes known to harbour mutations that cause EB. The analysis revealed that two patients had the same mutation in the gene JUP.
The patients had shown the same symptoms in early infancy, including very fragile skin, thickened skin on the palms of the hands and soles of the feet, and hair loss that extended to the eyebrows and eyelashes. However, one patient was a two-and-a-half-year-old boy who only showed skin anomalies, and the other patient was a 22-year-old woman who also had a heart condition called arrhythmogenic right ventricular cardiomyopathy (ARVC).
"This is a serious disease that can require a heart transplant if the damage is too severe because of heart failure and life-threatening fast heart rhythms," said Dr. Reginald Ho, a cardiologist in the department of medicine at Sidney Kimmel Medical College in Philadelphia, and a co-author of the study.
In ARVC, rigid, fibrous tissue displaces healthy heart muscle over time, the study’s authors noted. As a result, the heart develops abnormal rhythms and becomes weak. According to the investigators, ARVC patients are vulnerable to heart failure and sudden cardiac death. Further, ARVC can be responsible for as much as 20% of sudden cardiac deaths in patients under 30, the researchers said. Many ARVC patients require an implantable defibrillator to manage life-threatening arrhythmias. Mutations in JUP that cause EB can also lead to stiffness of the heart muscle, and ARVC.
The study’s authors note the young boy in the study did not have heart problems yet, but the genetic findings suggest that he will develop them down the road.
"This means that with mutation analysis, you can predict when looking at EB patients at birth, whether they will have this very severe heart condition later in life," Dr. Uitto said. "These patients need to be monitored carefully for heart problems.”
Dr. Uitto and his team of researchers have been researching mutations in families with genetic skin disorders for three decades. He and his team have analyzed mutations in about 1,800 families around the world, searching for the genetic culprits behind skin conditions such as EB.
The findings published in Scientific Reports are just the latest for Dr. Uitto and his team. In 2019, the researchers found that patients with ichthyosis can develop liver problems later in life that can be severe enough to require a transplant.
"We are looking to identify new genes behind skin diseases like EB and ichthyosis," Dr. Uitto said. "By looking at patients' symptoms and family history, we have uncovered something completely unexpected."
"Together, these studies show how skin can help predict severe medical problems.”