When an infant has a life-threatening condition, it’s critical to rapidly and accurately identify if the cause is a genetic mutation. Sequencing one’s entire genome, also called whole genome sequencing (WGS), has become an important tool for identifying all possible disease-causing mutations. Despite its advantages, WGS has been mostly relegated to scientific research and hasn’t yet been widely adopted by doctors. A more popular technology is targeted gene panels, which sequence a limited number of genes with a known relationship to genetic disorders; they’re also more often covered by insurance.

In a new study, researchers from hospitals across the country studied 400 hospitalized infants, and compared WGS and a targeted gene panel that covers more than 1,700 genes. The WGS results provided a possible disease-causing mutation in a much higher percentage of the infants than gene panels (49% vs. 27%). Most of this increase was because WGS found more complex mutations or mutations in parts of the genome not covered by the panel. In other cases however, both technologies identified a given mutation, but whether that mutation was labeled as potentially dangerous was different, something that shouldn’t depend on the technology. The turnaround time for WGS was also a little more than for the gene panel (median 6.1 days vs. 4.2 days), though this difference was a lot smaller for a subset of urgent cases.

This study is important evidence for the usefulness of WGS in such a critical situation. Even though the results point to a need for uniformity in how an already identified mutation gets labeled as dangerous, WGS demonstrated a clear increase in the number of concerning mutations found. The authors hope that their research will convince insurance providers to take advantage of the decreasing costs of sequencing and make WGS standard care.

Jill Maron is a Professor of Pediatrics at Brown University and the Chief of Pediatrics at Women & Infants Hospital in Providence, RI. The Genomic Medicine for Ill Neonates and Infants (GEMINI) Study is a research initiative sponsored by Tufts Medical Center (Boston, MA), collaborating with Rady Children’s Hospital (San Diego, CA), Children’s Hospital Medical Center (Cincinnati, OH), Mount Sinai Hospital (New York, NY), North Carolina Children’s Hospital (Chapel Hill, NC), and Children’s Hospital of Pittsburgh (Pittsburgh, PA).

Managing Correspondent: Alex Yenkin

Press Article: “Infant Rapid Genome Sequencing Yields More Diagnoses Than Targeted Gene Panels, Study Finds,” GenomeWeb

Original Article: “Rapid Whole-Genomic Sequencing and a Targeted Neonatal Gene Panel in Infants With a Suspected Genetic Disorder,” JAMA

Image Credit: pxhere