GEMINI Study Reveals Diagnostic Advantages for Whole-Genome Sequencing in Hospitalized Infants

Newborn baby’s feet at a hospital. (Shutterstock)

December 15, 2023

Diagnosing possible genetic disorders quickly in hospitalized infants can be challenging. Narrowing the search to a small group of genes can speed diagnostic results but may cause doctors to miss some disease-causing genetic changes. Sequencing all genes can catch more disease-causing variants but may slow diagnostic results. NCATS funded a study comparing broad and narrow genomic testing. The results of the study could help doctors choose the right testing options for their patients.

The Genomic Medicine in Ill Infants and Newborns (GEMINI) study compared whole-genome sequencing (WGS) with targeted gene sequencing. GEMINI researchers at Women & Infants Hospital of Rhode Island worked with partners at nine other centers. Together, they measured how many disease-causing or suspicious gene variants each approach identified. They also measured how long it took to get the test results and how the tests shaped treatment decisions.

GEMINI included 400 infants younger than 1 year who were hospitalized with a possible genetic disorder. Six medical centers enrolled participants in the study. The researchers tested each infant using both WGS and targeted gene sequencing. The targeted test focused on 1,722 genes linked with disorders that usually appear early in childhood. The WGS method sought to provide sequence information for the approximately 25,000-30,000 genes in the human genome.

More than half of the infants (51%) had at least one causal or suspicious gene variant found by one of the tests. WGS revealed nearly twice as many genetic variants as targeted testing. WGS identified variants in 49% of the infants, compared with 27% using the narrower targeted test. In 95 infants, WGS led to a diagnosis that targeted gene sequencing missed. That number was nearly 10 times greater than the nine diagnoses that targeted gene sequencing caught that WGS missed.

Targeted gene sequencing did have a speed advantage over WGS for routine testing. The median time to return test results was 100.3 hours for targeted gene sequencing. That topped the median 146.6 hours for WGS. However, for 107 urgent cases in which infants were critically ill, WGS returned results at a median of 79.9 hours, compared with 98.5 hours for targeted gene sequencing.

After the tests, doctors changed their approaches to medical, surgical and/or nutritional management in 19% of patients. More than three in four doctors (76%) said they found genomic sequencing to be useful or very useful.

The GEMINI researchers said their study’s results support the need to have genomic sequencing tests widely available and covered by public and private health insurers.

Learn more about the study findings in JAMA.

The research was supported by CTSA Program Collaborative Innovation Award (CCIA) grant U01TR002271.