A September 26 article in Proceedings of the National Academy of Science (PNAS) explains how a medical team at Stanford University School of Medicine solved a genetic riddle, with a significant contribution from the lab of Dr. Natalia Trayanova, Murray B. Sachs Professor of Biomedical Engineering and core faculty member of the Institute for Computational Medicine.

The PNAS paper entitled, “Early somatic mosaicism is a rare cause of long-QT syndrome,” describes the case of baby Astrea, who was diagnosed at birth with long QT syndrome, a disorder of the heart’s electrical activity that causes sudden, uncontrollable, and dangerous arrhythmias. The underlying cause, however, was unknown. A collaboration of Stanford clinicians and researchers, led by Professor of Medicine and of Genetics Euan Ashley and pediatric cardiologist James Priest, determined through rapid whole-genome sequencing that Astrea was a “mosaic” individual – 92 percent of the cells in her body were healthy, 8 percent defective. Genetic sequencing of Astra and her parents verified the mutation.

The Stanford researchers could not be certain that the mutation extended to Astrea’s heart, but by 7 months of age her heart had enlarged despite medications, an implanted defibrillator, and a pacemaker. Astrea received a heart transplant before her first birthday. The Stanford team retained tissue from her original heart and confirmed that it contained 8 percent mutant cells. The final question was whether that relatively small percentage of mutant heart cells could cause severe long QT syndrome. To find out, the Stanford team turned to Dr. Trayanova’s Computational Cardiology Laboratory in ICM. Dr. Trayanova, Assistant Research Professor of Biomedical Engineering Patrick M. Boyle, and BME graduate assistant Joseph K. Yu developed a computer model of infant Astrea’s heart. It behaved precisely as Astrea’s real heart had. “It was an important moment: a mosaic heart really could cause heart block and cardiac arrest,” said Stanford’s Ashley. Dr. Priest believes this work may have provided new tools for determining the cause for some 30 percent of heart arrhythmia patients who lack a genetic diagnosis, as well as for genetic diseases elsewhere in the body.

A more detailed article on baby Astrea’s case can be found on Stanford Medicine’s website.