12/22/2025
Recent research by Shaobo Zhang, MD, Evan A. Rajadhyaksha, MD, and co-authored by Riley Children’s Health physician-scientists and pediatric nephrologists David Hains, MD, MBA and Andrew Schwaderer, MD, has validated digital droplet PCR (ddPCR) for detecting copy number variations (CNVs)—deletions or duplications of DNA segments crucial for diagnosing many genetic disorders.
This new study, published by Scientific Reports, builds on previous discoveries from their lab linking CNVs to susceptibility to urinary tract infections (UTIs) in children with vesicoureteral reflux (VUR). Until now, testing for these gene variations has been challenging, with traditional methods often falling short in accuracy and scalability. The main problem in DNA copy number variations in medicine is that to accurately determine copy numbers, clinical labs typically rely on methods that are extremely time intensive, require specialized equipment, and demand significant scientific expertise—making them impractical for routine use.
“Genetic variations can shape how patients respond to disease, and understanding these differences is key to delivering truly personalized care,” said Dr. Hains, who is the division chief of pediatric nephrology at Riley Children’s. “Our team’s recent work verifying digital droplet PCR paves the way for more cost-effective and rapid genetic risk profiling for children with conditions like vesicoureteral reflux.”
Unlike older CNV genetic testing techniques, ddPCR delivers precise measurement of the concentration of a target molecule, ensuring reliable results even when copy numbers are high, a critical advantage for clinical decision-making. Importantly, ddPCR can be implemented in any clinical lab, costs dollars per sample, and produces results within hours—all while delivering extremely accurate and precise measurements.
With its high throughput and cost-effectiveness, ddPCR is poised to make testing for copy number variations more accessible in routine care. In the new study, ddPCR matched results from the gold-standard pulsed-field gel electrophoresis (PFGE) with 95% accuracy, far surpassing conventional quantitative PCR (qPCR), which achieved only 60% agreement.
“Our research findings confirm that ddPCR delivers both accuracy and practicality for clinical use,” said Dr. Andrew Schwaderer. “It maintained precision across a wide range of copy numbers—even at high copy numbers where qPCR faltered—addressing a major gap in current genetic testing and opening the door to expanded applications to a number of genetic variations for children and their disease courses.”
For children with VUR, understanding genetic risk factors like CNVs could guide more targeted interventions and improve outcomes. Digital droplet PCR offers clinicians a reliable, scalable solution that brings pediatric care closer to true precision medicine. With these findings and future research into broader genomic applications, ddPCR has the potential to become a cornerstone technology for accurate, cost-effective, and scalable genomic testing in clinical practice.
Learn more about Riley Children’s Health pediatric nephrology program, research and clinical breakthroughs in the annual report.
