MMI contributes to study on whole genome sequencing

For nearly three years, Kristen Fishler, a genetic counselor at the Munroe-Meyer Institute Department of Genetics, and her colleagues at UNMC and MMI, have been working with sites across the country to document the impact of whole-genome sequencing (WGS) as a diagnostic tool for acutely ill infants with a suspected genetic disease.

MMI was part of a study sponsored by Illumina and led by Ryan Taft, PhD, Illumina’s chief of scientific research.

On Sept. 27, the research was published in the JAMA Pediatrics Journal. Results of the study, which examined more than 350 infants, showed that WGS positively impacted vulnerable infants in a Level IV NICU.

Fishler and her colleagues hope that the comprehensive study, published in a major journal, will begin to shift attitudes in the insurance industry, where most currently do not cover WGS.

"Data like this will help make the case that they should start covering it," Fishler said.

Using WGS as a diagnostic tool not only doubled the successful diagnosis rate but resulted in changes to the infants’ clinical care management. According to the study, "introduction of WGS was associated with a significant increase in focused clinical management compared with usual care. Access to first-line WGS may reduce health care disparities by enabling diagnostic equity."

"This is an important result for infants and vulnerable populations," Fishler said. "And after this study has encompassed most of my three-year career here at MMI and UNMC, I continue to have an interest in exploring ways to provide access to genetic evaluation and testing for these vulnerable infants."

Working as part of a national effort, MMI was the second-largest recruiting institution site, Fishler said — a point of pride for the team.

Additionally, previous research historically has not included premature infants, on the argument that if symptoms could be attributed to prematurity, the infants should be excluded — "but there was a large group of premature infants that received diagnoses in this study cohort," Fishler said. "More premature infants should be included in these studies going forward."

The majority of participants who were enrolled in the study had multiple congenital anomalies. Other common features of infants who were enrolled included an isolated congenital anomaly or neurological condition.

"In many cases, a syndrome was identified for the patient that provided the cause for their constellation of symptoms," she said.

Results also included secondary findings that are associated with adult-onset conditions, such as cancer or heart problems.

"Five percent of our population had these findings, and that’s higher than what we’ve seen in other studies, where it’s usually 1-2 percent," Fishler said. "These findings impact the potential immediate health care of the parents, she said, one or both of whom could also carry the same variant. Many of these conditions include recommendations for preventive management (screening, etc.) starting in the 30s. Many of our patients' parents are in this age category, making these results important for screening management."

"Finally, there were pharmocogenomic results, which provide info on whether an individual may respond to certain drugs. And again, this has implications for the parents. Even in lieu of diagnostic results for their infant, parents were often happy to walk away with this information, empowered to bring it to their doctor and start a conversation."

Fishler and Omar Rahman, MD, director of the MMI Department of Genetics, credited the study team, which included members of the MMI genetics department and Children’s Hospital & Medical Center neonatology division, including study principal investigator Luca Brunelli, MD, now at the University of Utah.

For Fishler, the study is further evidence of the value of WGS testing and a reason for insurance companies to begin covering it.

Grant funding, already in-hand, will allow for continued research on this issue.