RARE Daily

Clinical RNA Sequencing Helps Interpret Genome Sequencing to Reach Rare Diagnosis

April 14, 2023

Rare Daily Staff

A new clinical RNA sequencing platform at The Hospital for Sick Children is helping to facilitate research into rare genetic conditions and helping to diagnose children with complex genetic conditions.

While DNA sequencing offers a view of the genetic code of an individual, RNA sequencing provides insights into how the body puts that code into action to show what proteins are being made.

The SickKids Research Institute over the last six years has been working to incorporate RNA sequencing into the research pipeline. SickKids said it is now, for the first time in Canada, validated to be used as a clinical diagnostic tool.

“The clinical RNA sequencing platform at SickKids is helping to move the needle in achieving a diagnosis for patients with rare genetic conditions through patient-centered care, or what SickKids calls Precision Child Health,” said Lianna Kyriakopoulou, clinical laboratory director in the division of genome diagnostics at SickKids. “Used together, genome sequencing and RNA sequencing can potentially further inform which findings are relevant to help guide clinical decision-making.”

Using this clinical RNA sequencing platform, a team of SickKids researchers, in collaboration with researchers at Brock University, performed genome sequencing and RNA sequencing on 97 individuals from 39 different families in the Complex Care Program, a clinical program focused on diagnosis and care of children with unexplained medical complexity.

In a study published in the American Journal of Human Genetics, the RNA analysis provided useful diagnostic information for an additional 8 percent of the patients whose diagnosis was not confirmed using genome sequencing alone, either confirming or ruling out the impact of a DNA variant identified during genome sequencing.

“Our findings demonstrate a clear benefit to pairing RNA sequencing with genome sequencing in a cohort of children who are suspected to have a genetic diagnosis,” said co-first author Ashish Deshwar, a resident physician in Medical Genetics and Genomics.

This study is one of the first to examine the utility of a trio-approach to RNA sequencing, a process which involves conducting RNA sequencing on the affected individual and both parents. While trio RNA sequencing with this population did not uncover any new genetic variants, it decreased the amount of time researchers needed to spend reviewing results and made the analysis more efficient.

The scientists said as more research is done into the benefits of RNA sequencing, they will be able to better define the scenarios where clinical RNA sequencing can provide real insights for patients.

Photo: Clinical Laboratory Director in the Division of Genome Diagnostics of Sickkids Lianna Kyriakopoulou  and Laboratory Specialist Kyoko Yuki

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