BOSTON, July 11, 2023 – A new study from Tufts Medical Center indicates that whole genome sequencing (WGS) is nearly twice as effective as a targeted gene sequencing test at diagnosing genetic disorders in newborns and infants. These findings offer a substantial leap forward in the early identification and treatment of such disorders.
The research, dubbed the Genomic Medicine for Ill Neonates and Infants (GEMINI) Study, was first published in The Journal of the American Medical Association (JAMA). It enrolled 400 infants under the age of one year, all of whom exhibited a range of suspected but undiagnosed genetic disorders. The subjects were located at six centers across the United States, and each received both a WGS and a targeted gene sequencing test known as NewbornDx.
Whole genome sequencing, capable of identifying variants in all 20,000 genes in the human body, detected a genetic disorder in 49 percent of the patients. The NewbornDx, which can identify variants in 1,722 genes linked to newborn and infant genetic disorders, identified a genetic disorder in only 27 percent of the participants. The NewbornDx missed 40 percent of diagnoses that WGS managed to capture, and 134 new genetic diagnoses were found that had never before been described. In total, 51 percent of the study's patients were diagnosed with a genetic disorder through either test.
“More than half of the babies in our study had a genetic disorder that would have remained undetected at most hospitals across the country if not for genome sequencing technologies,” said Dr. Jonathan Davis, Chief of Newborn Medicine at Tufts Medical Center and Co-Principal Investigator of the study. He asserted that an early diagnosis of an infant's genetic disorder helps ensure they receive the best possible medical care and reinforced WGS as the gold standard for the diagnosis of such disorders.
However, the study also revealed some downsides to WGS. The method took approximately two days longer to deliver routine results than the targeted gene sequencing test, and the latter was found to be less costly. Furthermore, as the targeted test screens only for specific disorders that occur in newborns and infants, it avoids unintentionally revealing potential health risks that might appear later in life.
The researchers noted another concern: the absence of standardization in neonatal genetics interpretation. There were discrepancies among laboratories in 40 percent of cases about whether a recognized gene abnormality was indeed the cause of a suspected genetic disorder.
Dr. Jill Maron, Chief of Pediatrics at Women & Infants Hospital of Rhode Island and Co-Principal Investigator of the study, highlighted the variety of approaches and lack of consensus among geneticists. She was, however, optimistic about the cost-effectiveness of genome sequencing in this at-risk population, expressing support for insurance coverage for these tests.
Dr. Stephen F. Kingsmore, President and CEO of Rady Children's Institute for Genomic Medicine and a co-investigator of the study, concluded, "This study provides further evidence that genetic disorders are common among newborns and infants. The findings strengthen support for early diagnosis by rapid genomic sequencing, allowing for the use of precision medicine to better care for this vulnerable patient population."
The research, dubbed the Genomic Medicine for Ill Neonates and Infants (GEMINI) Study, was first published in The Journal of the American Medical Association (JAMA). It enrolled 400 infants under the age of one year, all of whom exhibited a range of suspected but undiagnosed genetic disorders. The subjects were located at six centers across the United States, and each received both a WGS and a targeted gene sequencing test known as NewbornDx.
Whole genome sequencing, capable of identifying variants in all 20,000 genes in the human body, detected a genetic disorder in 49 percent of the patients. The NewbornDx, which can identify variants in 1,722 genes linked to newborn and infant genetic disorders, identified a genetic disorder in only 27 percent of the participants. The NewbornDx missed 40 percent of diagnoses that WGS managed to capture, and 134 new genetic diagnoses were found that had never before been described. In total, 51 percent of the study's patients were diagnosed with a genetic disorder through either test.
“More than half of the babies in our study had a genetic disorder that would have remained undetected at most hospitals across the country if not for genome sequencing technologies,” said Dr. Jonathan Davis, Chief of Newborn Medicine at Tufts Medical Center and Co-Principal Investigator of the study. He asserted that an early diagnosis of an infant's genetic disorder helps ensure they receive the best possible medical care and reinforced WGS as the gold standard for the diagnosis of such disorders.
However, the study also revealed some downsides to WGS. The method took approximately two days longer to deliver routine results than the targeted gene sequencing test, and the latter was found to be less costly. Furthermore, as the targeted test screens only for specific disorders that occur in newborns and infants, it avoids unintentionally revealing potential health risks that might appear later in life.
The researchers noted another concern: the absence of standardization in neonatal genetics interpretation. There were discrepancies among laboratories in 40 percent of cases about whether a recognized gene abnormality was indeed the cause of a suspected genetic disorder.
Dr. Jill Maron, Chief of Pediatrics at Women & Infants Hospital of Rhode Island and Co-Principal Investigator of the study, highlighted the variety of approaches and lack of consensus among geneticists. She was, however, optimistic about the cost-effectiveness of genome sequencing in this at-risk population, expressing support for insurance coverage for these tests.
Dr. Stephen F. Kingsmore, President and CEO of Rady Children's Institute for Genomic Medicine and a co-investigator of the study, concluded, "This study provides further evidence that genetic disorders are common among newborns and infants. The findings strengthen support for early diagnosis by rapid genomic sequencing, allowing for the use of precision medicine to better care for this vulnerable patient population."