Scientists have identified a possible cause of a rare and dangerous genetic heart disorder known as Short QT syndrome. The condition is linked to abnormal electrical activity in the heart and can lead to sudden death at a young age.

The study findings were published in the European Heart Journal.

An international team of researchers, including specialists from Germany, discovered that one possible cause of the disease is associated with mutations in the SLC4A3 gene. This gene is responsible for the exchange of bicarbonate and chloride inside cells.

The heart functions through a highly precise electrical balance: ions such as calcium and sodium constantly move in and out of cells, enabling rhythmic contractions. In Short QT syndrome, this balance is disrupted — the heart “recharges” too quickly between beats.

The scientists studied two previously unknown mutations of this gene and created a laboratory model of human heart cells. They also used CRISPR technology to “correct” the mutations and compare healthy and altered cells.

The results were significant: the mutations were found to affect the pH level inside the cells, causing it to rise. This, in turn, triggered a chain of changes:

  • ion flow became disrupted

  • calcium current decreased

  • sodium-calcium exchange increased

  • the electrical cycle of heart cells became shorter

As a result, the heart began to function unstably and with a dangerously accelerated rhythm.

The researchers believe that the process starts with a disruption of the acid-base balance inside the cell, which then causes the entire electrical system of the heart to break down.

The good news is that some existing medications — including the antiarrhythmic drugs Quinidine and Sotalol — were able to partially normalize cell function in experiments and reduce the frequency of arrhythmias.

This discovery is important for the future of personalized medicine, as it helps scientists better understand why the disease develops and how treatments can be more accurately tailored for patients with specific genetic variants.