Testing the entire genome is twice as effective as targeted tests in identifying genetic disorders.

Testing the entire genome is twice as effective as targeted tests in identifying genetic disorders.

Whole Genome Sequencing: A Game-Changer for Diagnosing Genetic Disorders in Newborns

Finding genetic disorders in newborns and infants is crucial for providing them with the care they need. However, a recent study has shown that one approach, whole genome sequencing (WGS), is far superior to targeted gene-sequencing in identifying abnormalities that lead to disorders. Although WGS takes longer to obtain results, it was found to be nearly twice as effective as targeted gene-sequencing.

Dr. Jonathan Davis, chief of newborn medicine at Tufts Medical Center in Boston and co-author of the study, emphasized the importance of early diagnosis: “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. Successfully diagnosing an infant’s genetic disorder as early as possible helps ensure they receive the best medical care.”

To investigate this further, the Genomic Medicine for Ill Neonates and Infants (GEMINI) Study enrolled 400 newborns and infants under the age of one who had a variety of suspected but undiagnosed genetic disorders. These infants were seen at six centers across the United States, including Tufts Medical Center.

Each child received both whole genome sequencing and a commercially available targeted gene sequencing test called NewbornDx. While WGS can identify variants in all 20,000 genes in the human body, NewbornDx focuses on 1,722 genes known to be linked to genetic disorders in babies.

The results were fascinating. WGS detected a genetic disorder in 49% of patients, while the targeted gene sequencing test only identified a genetic disorder in 27% of the patients, missing 40% of the diagnoses that WGS captured. Additionally, the researchers discovered 134 new genetic diagnoses that had never before been described. Overall, 51% of patients in the study were diagnosed with a genetic disorder using either test.

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Dr. Stephen Kingsmore, president and CEO of Rady Children’s Institute for Genomic Medicine in San Diego, expressed the significance of these findings: “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.”

While genome sequencing can be costly, its ability to provide highly informative results outweighs the expense. Therefore, the researchers advocate for ongoing efforts to have these tests covered by insurance.

However, it’s important to consider the downsides of whole genome sequencing. Compared to NewbornDx, it took six days to obtain results with WGS, which may cause anxiety for parents awaiting a diagnosis. Additionally, the targeted test is less expensive and screens only for specific genetic disorders that appear in newborns and infants. It avoids unintentionally revealing potential future health risks that the child’s parents may not want to know, such as risks for Alzheimer’s disease or cancer.

The study also highlighted a concern regarding the lack of standardization in neonatal genetics interpretation. In 40% of cases, different labs disagreed about whether a mutually acknowledged gene abnormality was the cause of the suspected genetic disorder. This emphasizes the need for further research and development to streamline the interpretation process and minimize discrepancies.

In conclusion, whole genome sequencing has emerged as the gold standard for accurately diagnosing genetic disorders in newborns and infants. Its effectiveness in identifying abnormalities far surpasses targeted gene-sequencing, leading to better medical care for these vulnerable patients. Ongoing efforts to make WGS more accessible and covered by insurance are essential to ensure early diagnosis and use of precision medicine. Nevertheless, challenges such as longer wait times for results and the potential revelation of future health risks still need to be addressed. With continued advancements and standardization in neonatal genetics, the future of diagnosing genetic disorders in newborns looks promising.

Source: Tufts University, news release, July 11, 2023